Journal articles: 'SOD1 gene'

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Lian, Shanshan, Liang Zhao, Xiaogang Xun, Jiarun Lou, Moli Li, Xu Li, Shi Wang, Lingling Zhang, Xiaoli Hu, and Zhenmin Bao. "Genome-Wide Identification and Characterization of SODs in Zhikong Scallop Reveals Gene Expansion and Regulation Divergence after Toxic Dinoflagellate Exposure." Marine Drugs 17, no. 12 (December 12, 2019): 700. http://dx.doi.org/10.3390/md17120700.

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As filter-feeding animals mainly ingesting microalgae, bivalves could accumulate paralytic shellfish toxins (PSTs) produced by harmful algae through diet. To protect themselves from the toxic effects of PSTs, especially the concomitant oxidative damage, the production of superoxide dismutase (SOD), which is the only eukaryotic metalloenzyme capable of detoxifying superoxide, may assist with toxin tolerance in bivalves. To better understand this process, in the present study, we performed the first systematic analysis of SOD genes in bivalve Chlamys farreri, an important aquaculture species in China. A total of six Cu/Zn-SODs (SOD1-6) and two Mn-SODs (SOD7, SOD8) were identified in C. farreri, with gene expansion being revealed in Cu/Zn-SODs. In scallops exposed to two different PSTs-producing dinoflagellates, Alexandrium minutum and A. catenella, expression regulation of SOD genes was analyzed in the top ranked toxin-rich organs, the hepatopancreas and the kidney. In hepatopancreas, which mainly accumulates the incoming PSTs, all of the six Cu/Zn-SODs showed significant alterations after A. minutum exposure, with SOD1, 2, 3, 5, and 6 being up-regulated, and SOD4 being down-regulated, while no significant change was detected in Mn-SODs. After A. catenella exposure, up-regulation was observed in SOD2, 4, 6, and 8, and SOD7 was down-regulated. In the kidney, where PSTs transformation occurs, SOD4, 5, 6, and 8 were up-regulated, and SOD7 was down-regulated in response to A. minutum feeding. After A. catenella exposure, all the Cu/Zn-SODs except SOD1 were up-regulated, and SOD7 was down-regulated in kidney. Overall, in scallops after ingesting different toxic algae, SOD up-regulation mainly occurred in the expanded Cu/Zn-SOD group, and SOD6 was the only member being up-regulated in both toxic organs, which also showed the highest fold change among all the SODs, implying the importance of SOD6 in protecting scallops from the stress of PSTs. Our results suggest the diverse function of scallop SODs in response to the PST-producing algae challenge, and the expansion of Cu/Zn-SODs might be implicated in the adaptive evolution of scallops or bivalves with respect to antioxidant defense against the ingested toxic algae.

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Ściskalska, Milena, Monika Ołdakowska, Grzegorz Marek, and Halina Milnerowicz. "Changes in the Activity and Concentration of Superoxide Dismutase Isoenzymes (Cu/Zn SOD, MnSOD) in the Blood of Healthy Subjects and Patients with Acute Pancreatitis." Antioxidants 9, no. 10 (October 1, 2020): 948. http://dx.doi.org/10.3390/antiox9100948.

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This study was aimed at evaluating the changes in the concentration and activity of all superoxide dismutase isoenzymes (SOD1, SOD2, SOD3) in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartment. The relationships between the activity/concentration of SODs, metal concentration and the markers of inflammation were evaluated. To assess the pro/antioxidative imbalance, the malonyldialdehyde (MDA) concentration and the value of total antioxidant capacity (TAC) were measured. The impact of single-nucleotide polymorphism (SNP) in the SOD1 gene (rs2070424) on the activity/concentration of SOD1 as the main isoenzyme of the SOD family was also analyzed in this study. The SOD2 activity in erythrocytes was increased compared to plasma: 10-fold in the AP patient group and 5-fold in healthy subjects. The plasma of AP patients showed an increased SOD1 concentration and decreased SOD2 and SOD3 concentrations compared to healthy subjects. The Cu/Zn SOD (SOD1 + SOD3) concentration in plasma of AP patients was elevated compared to healthy subjects, but changes in plasma Cu/Zn SOD (SOD1 + SOD3) activity in the examined groups were not observed. An influence of SNP rs2070424 in the SOD1 gene on the total activity of SOD in AP patients (with AG genotype), accompanied by an increased IL-6 concentration, was observed. In oxidative stress conditions induced by inflammation, the participation of individual forms of plasma SOD isoenzymes in total antioxidative activity of SOD changed. A significant increase in the intracellular SOD1 concentration in plasma of AP patients proves the important role of this isoenzyme in the neutralization of oxidative stress induced by impaired Cu and Zn homeostasis. The presence of increased concentration of SOD2 in erythrocytes of healthy subjects and AP patients confirms the important function of this isoenzyme in the antioxidative defense.

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Tuna, A., G. Ozturk, TB Gerceker, E. Karaca, H. Onay, SM Guvenc, and O. Cogulu. "Superoxide dismutase 1 and 2 gene polymorphism in Turkish vitiligo patients." Balkan Journal of Medical Genetics 20, no. 2 (December 29, 2017): 67–73. http://dx.doi.org/10.1515/bjmg-2017-0033.

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Abstract Vitiligo is an acquired disease of unknown etiology. Several theories have been proposed to understand the pathogenesis. The role of oxidative stress has been getting more important in recent years. One of the primary antioxidant enzymes in vitiligo is the superoxide dismutase (SOD). The aim of this study is to investigate the polymorphisms of the SOD1 and SOD2 in Turkish vitiligo patients. One hundred one vitiligo patients and 99 healthy controls without family history of vitiligo were included into the study. The SOD1 35 A/C and SOD2 A16V (C/T) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphim (PCR-RFLP). Vitiligo patients and control group of SOD1 35 A/C and SOD2 A16V (C/T) polymorphism allele frequencies were compared by using χ2 tests. The distribution of the SOD1 35 AA and AC genotypes were similar in vitiligo patients and control group. When the patient and the control groups were compared for the SOD2 Ala9Val (C/T) polymorphism, a significant difference was determined for the distribution of the genotypes [p = 0.047, odds ratio (OR) = 2.075, 95% confidence interval (95% CI) = 1.008-4.272]. The relative risk for development of vitiligo was found as a 2-fold increase in the TT genotype. The increase of TT homozygosity in the vitiligo cases creates the problem on the transfer of the enzyme to the mitochondria and thus, the SODs antioxidant effect may decrease in vitiligo but the polymorphism was not determined in all patients, so this study needs to be substantiated by other studies containing a higher number of patients.

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Kim, Sang-Hoon, Sang-Heon Kim, Jae-Hyoung Lee, Byoung-Hoon Lee, Ho Joo Yoon, Dong Ho Shin, Sung Soo Park, Suk Bin Jang, Jae-Seuk Park, and Young-Koo Jee. "Superoxide Dismutase Gene (SOD1, SOD2, and SOD3) Polymorphisms and Antituberculosis Drug-induced Hepatitis." Allergy, Asthma & Immunology Research 7, no. 1 (2015): 88. http://dx.doi.org/10.4168/aair.2015.7.1.88.

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Kotowska, Jadwiga, and Ewa Jówko. "Effect of Gene Polymorphisms in Antioxidant Enzymes on Oxidative-Antioxidative Status in Young Men." Polish Journal of Sport and Tourism 27, no. 4 (December 1, 2020): 7–13. http://dx.doi.org/10.2478/pjst-2020-0020.

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Abstract Introduction. The aim of the study was to evaluate the relationship between SOD1 +35A/C, SOD2 Val16Ala and GPx1 Pro198Leu gene polymorphisms and baseline level of oxidative-antioxidative status in blood. Material and methods.The study included 154 male students of physical education who participated in practical classes included in the study curriculum. Genotyping was carried out on genomic DNA using real-time PCR reaction with TaqMan assays. Also, fasting blood samples were analyzed for biochemical parameters including superoxide dismutase (SOD) activity in erythrocytes and the activity of glutathione peroxidase (GPx) in whole blood, as well as serum concentration of lipid hydroperoxides (LOOHs) and total antioxidant capacity (TAC) of serum. Results. SOD2 polymorphism had a significant effect on serum LOOHs concentration. Individuals with Val/Val genotype presented a significantly higher level of LOOHs than Val/Ala genotype carriers (p < 0.05). In addition, no significant differences in SOD and GPx activity or TAC were found between SOD2 genotypes. Apart from the SOD2 polymorphism, no significant influence of both SOD1 and GPx1 polymorphisms on measured biochemical parameters was found, probably due to the lack of mutant homozygous genotypes in the study group. Conclusions. In young, healthy and physically active men, SOD2 polymorphism has an influence on the resting level of oxidative stress marker in the blood without affecting both enzymatic and non-enzymatic antioxidant defence. In turn, SOD1 and GPx1 polymorphisms do not seem to affect oxidative-antioxidative status. However, the absence of SOD1 CC and GPx1 Leu/Leu may indicate that these genotypes are disadvantageous, and thus underrepresented in young, healthy and physically fit population.

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Cao, Xueli, Yujuan Sun, Yanfei Lin, Yanjun Pan, Umer Farooq, Lan Xiang, and Jianhua Qi. "Antiaging of Cucurbitane Glycosides from Fruits of Momordica charantia L." Oxidative Medicine and Cellular Longevity 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/1538632.

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Methanol extracts of Momordica charantia L. fruits are extensively studied for their antiaging activities. A new cucurbitane-type triterpenoid (1) and nine other known compounds (2–10) were isolated, and their structures were determined according to their spectroscopic characteristics and chemical derivatization. Biological evaluation was performed on a K6001 yeast bioassay system. The results indicated that all the compounds extended the replicative lifespan of K6001 yeast significantly. Compound 9 was used to investigate the mechanism involved in the increasing of the lifespan. The results indicated that this compound significantly increases the survival rate of yeast under oxidative stress and decreases ROS level. Further study on gene expression analysis showed that compound 9 could reduce the levels of UTH1 and SKN7 and increase SOD1 and SOD2 gene expression. In addition, it could not extend the lifespan of the yeast mutants of Uth1, Skn7, Sod1, and Sod2. These results demonstrate that compound 9 exerts antiaging effects via antioxidative stress and regulation of UTH1, SKN7, SOD1, and SOD2 yeast gene expression.

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Bonder, Claudine S., Derrice Knight, Daniel Hernandez-Saavedra, Joe M. McCord, and Paul Kubes. "Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 3 (September 2004): G676—G684. http://dx.doi.org/10.1152/ajpgi.00049.2004.

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After an ischemic episode, reperfusion causes profound oxidative stress in the vasculature of the afflicted tissue/organ. The dysregulated accumulation of reactive oxygen species (ROS), such as superoxide, has been closely linked to the production and release of proinflammatory mediators, a profound increase in adhesion molecule expression by the vascular endothelium, and infiltration of neutrophils during ischemia-reperfusion (I/R). Superoxide dismutase (SOD) has been shown to protect tissues and organs against I/R-induced injury; however, the drug had to be continuously perfused or kidneys had to be occluded to prevent clearance. We used intravital microscopy, a system that allowed us to visualize neutrophil-endothelial interactions within the mesenteric postcapillary venules of cats subjected to I/R and tested the hypothesis that I/R-induced neutrophil recruitment was inhibited by treatment with SOD2/3. SOD2/3 is a chimeric fusion gene product that contains the mature SOD2 as well as the COOH-terminal “tail” of SOD3 and, unlike the three naturally occurring SODs (SOD1, SOD2, and SOD3), which bear a net negative charge at pH 7.4, SOD2/3 is positively charged and physiologically stable. Our results suggest that not only does SOD2/3 have a much greater efficacy in vivo than the native human SOD2, but its administration prevents I/R-induced neutrophil-endothelial cell interactions and microvascular dysfunction. Moreover, our data support the hypothesis that reactive oxidants mediate I/R-induced injury and that the chimeric recombinant SOD2/3 has the potential to be a therapeutic agent against this debilitating illness.

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Lisse, Thomas S. "Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer." Applied Sciences 10, no. 7 (April 8, 2020): 2554. http://dx.doi.org/10.3390/app10072554.

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Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. First, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10 nM but not at 100 nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 h of 10 nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 ours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

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Muratet, François, Elisa Teyssou, Aude Chiot, Séverine Boillée, Christian S. Lobsiger, Delphine Bohl, Beata Gyorgy, et al. "Impact of a frequent nearsplice SOD1 variant in amyotrophic lateral sclerosis: optimising SOD1 genetic screening for gene therapy opportunities." Journal of Neurology, Neurosurgery & Psychiatry 92, no. 9 (March 30, 2021): 942–49. http://dx.doi.org/10.1136/jnnp-2020-325921.

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ObjectiveMutations in superoxide dismutase 1 gene (SOD1), encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the production of these aberrant and deleterious SOD1 species, antisense oligonucleotide approaches have recently emerged and showed promising effects in clinical trials. To offer the possibility to any patient with SOD1-ALS to benefit of such a gene therapy, it is necessary to ascertain whether any variant of unknown significance (VUS), detected for example in SOD1 non-coding sequences, is pathogenic.MethodsWe analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.ResultsWe identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358–10T>G nearsplice SOD1 variant was corroborated based on its high frequency (as the second most frequent SOD1 variant) in French fALS, the segregation analysis confirmed in eight affected members of a large pedigree, the typical SOD1-related phenotype observed (with lower limb onset and prominent lower motor neuron involvement), and findings on postmortem tissues showing SOD1 misaccumulation.ConclusionsOur results highlighted nearsplice/intronic mutations in SOD1 are responsible for a significant portion of French fALS and suggested the systematic analysis of the SOD1 mRNA sequence could become the method of choice for SOD1 screening, not to miss these specific cases.

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Broom, Wendy J., Kristen E. Auwarter, Jake Ni, Deborah E. Russel, Li-An Yeh, Michele M. Maxwell, Marcie Glicksman, Aleksey G. Kazantsev, and Robert H. Brown. "Two Approaches to Drug Discovery in SOD1-Mediated ALS." Journal of Biomolecular Screening 11, no. 7 (September 14, 2006): 729–35. http://dx.doi.org/10.1177/1087057106290937.

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Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; approximately 25% of these cases are due to mutations in the Cu/Zn superoxide dismutase gene (SOD1). To date, 105 different mutations spanning all 5 exons have been identified in the SOD1 gene. Mutant SOD1-associated ALS is caused by a toxic gain of function of the mutated protein. Therefore, regardless of the specific mechanism whereby mutant SOD1 initiates motor neuron death, the authors hypothesize that measures that decrease levels of mutant SOD1 protein should ameliorate the phenotype in transgenic mice and potentially in patients with SOD1-mediated disease. They have designed 2 cell-based screening assays to identify small, brain-permeant molecules that inactivate expression of the SOD1 gene or increase the degradation of the SOD1 protein. Here they describe the development and optimization of these assays and the results of high-throughput screening using a variety of compound libraries, including a total of more than 116,000 compounds. The majority of the hit compounds identified that down-regulated SOD1 were shown to be toxic in a cell-based viability assay or were nonselective transcription inhibitors, but work is continuing on a number of nonspecific inhibitors of SOD1 expression. Ultimately, the authors believe that these 2 cell-based assays will provide powerful strategies to identify novel therapies for the treatment of inherited SOD1-associated forms of ALS.

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Udar, Nitin, Shari R. Atilano, Donald J. Brown, Bret Holguin, Kent Small, Anthony B. Nesburn, and M. Cristina Kenney. "SOD1: A Candidate Gene for Keratoconus." Investigative Opthalmology & Visual Science 47, no. 8 (August 1, 2006): 3345. http://dx.doi.org/10.1167/iovs.05-1500.

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Borel, Florie, Gwladys Gernoux, Huaming Sun, Rachel Stock, Meghan Blackwood, Robert H. Brown, and Christian Mueller. "Safe and effective superoxide dismutase 1 silencing using artificial microRNA in macaques." Science Translational Medicine 10, no. 465 (October 31, 2018): eaau6414. http://dx.doi.org/10.1126/scitranslmed.aau6414.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease caused by degeneration of motor neurons leading to rapidly progressive paralysis. About 10% of cases are caused by gain-of-function mutations that are transmitted as dominant traits. A potential therapy for these cases is to suppress the expression of the mutant gene. Here, we investigated silencing of SOD1, a gene commonly mutated in familial ALS, using an adeno-associated virus (AAV) encoding an artificial microRNA (miRNA) that targeted SOD1. In a superoxide dismutase 1 (SOD1)–mediated mouse model of ALS, we have previously demonstrated that SOD1 silencing delayed disease onset, increased survival time, and reduced muscle loss and motor and respiratory impairments. Here, we describe the preclinical characterization of this approach in cynomolgus macaques (Macaca fascicularis) using an AAV serotype for delivery that has been shown to be safe in clinical trials. We optimized AAV delivery to the spinal cord by preimplantation of a catheter and placement of the subject with head down at 30° during intrathecal infusion. We compared different promoters for the expression of artificial miRNAs directed against mutant SOD1. Results demonstrated efficient delivery and effective silencing of the SOD1 gene in motor neurons. These results support the notion that gene therapy with an artificial miRNA targeting SOD1 is safe and merits further development for the treatment of mutant SOD1-linked ALS.

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Boukaftane, Y., J. Khoris, B. Moulard, F. Salachas, V. Meininger, A. Malafosse, W. Camu, and G. A. Rouleau. "Identification of Six Novel SOD1 Gene Mutations in Familial Amyotrophic Lateral Sclerosis." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 25, no. 3 (August 1998): 192–96. http://dx.doi.org/10.1017/s0317167100034004.

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ABSTRACT:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SODl) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SODl mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protein.

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Jair, Herng-Woei, Hsu-Feng Lu, Yi-Wei Huang, Sz-Yun Pan, I.-Ling Lin, Hsin-Hui Huang, and Tsuey-Ching Yang. "Roles of the Two-MnSOD System of Stenotrophomonas maltophilia in the Alleviation of Superoxide Stress." International Journal of Molecular Sciences 20, no. 7 (April 10, 2019): 1770. http://dx.doi.org/10.3390/ijms20071770.

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Manganese-dependent superoxide dismutase (MnSOD, SodA) and iron-dependent SOD (FeSOD, SodB) are critical cytosolic enzymes for alleviating superoxide stress. Distinct from the singular sodA gene in most bacteria, Stenotrophomonas maltophilia harbors two sodA genes, sodA1 and sodA2. The roles of SodA1, SodA2, and SodB of S. maltophilia in alleviating superoxide stress were investigated. The expression of sod genes was determined by promoter–xylE transcriptional fusion assay and qRT–PCR. SodA2 and sodB expressions were proportional to the bacterial logarithmic growth, but unaffected by menadione (MD), iron, or manganese challenges. SodA1 was intrinsically unexpressed and inducibly expressed by MD. Complementary expression of sodA1 was observed when sodA2 was inactivated. The individual or combined sod deletion mutants were constructed using the gene replacement strategy. The functions of SODs were assessed by evaluating cell viabilities of different sod mutants in MD, low iron-stressed, and/or low manganese-stressed conditions. Inactivation of SodA1 or SodA2 alone did not affect bacterial viability; however, simultaneously inactivating sodA1 and sodA2 significantly compromised bacterial viability in both aerobic growth and stressed conditions. SodA1 can either rescue or support SodA2 when SodA2 is defective or insufficiently potent. The presence of two MnSODs gives S. maltophilia an advantage against superoxide stress.

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Fabrizio, Paola, Lee-Loung Liou, Vanessa N. Moy, Alberto Diaspro, Joan Selverstone Valentine, Edith Butler Gralla, and Valter D. Longo. "SOD2 Functions Downstream of Sch9 to Extend Longevity in Yeast." Genetics 163, no. 1 (January 1, 2003): 35–46. http://dx.doi.org/10.1093/genetics/163.1.35.

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Abstract Signal transduction pathways inactivated during periods of starvation are implicated in the regulation of longevity in organisms ranging from yeast to mammals, but the mechanisms responsible for life-span extension are poorly understood. Chronological life-span extension in S. cerevisiae cyr1 and sch9 mutants is mediated by the stress-resistance proteins Msn2/Msn4 and Rim15. Here we show that mitochondrial superoxide dismutase (Sod2) is required for survival extension in yeast. Deletion of SOD2 abolishes life-span extension in sch9Δ mutants and decreases survival in cyr1:mTn mutants. The overexpression of Sods—mitochondrial Sod2 and cytosolic CuZnSod (Sod1)—delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends survival by 30%. Deletion of the RAS2 gene, which functions upstream of CYR1, also doubles the mean life span by a mechanism that requires Msn2/4 and Sod2. These findings link mutations that extend chronological life span in S. cerevisiae to superoxide dismutases and suggest that the induction of other stress-resistance genes regulated by Msn2/4 and Rim15 is required for maximum longevity extension.

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Han, Eun-Soo, Florian L. Muller, Viviana I. Pérez, Wenbo Qi, Huiyun Liang, Liang Xi, Chunxiao Fu, et al. "The in vivo gene expression signature of oxidative stress." Physiological Genomics 34, no. 1 (June 2008): 112–26. http://dx.doi.org/10.1152/physiolgenomics.00239.2007.

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How higher organisms respond to elevated oxidative stress in vivo is poorly understood. Therefore, we measured oxidative stress parameters and gene expression alterations (Affymetrix arrays) in the liver caused by elevated reactive oxygen species induced in vivo by diquat or by genetic ablation of the major antioxidant enzymes CuZn-superoxide dismutase ( Sod1) and glutathione peroxidase-1 ( Gpx1). Diquat (50 mg/kg) treatment resulted in a significant increase in oxidative damage within 3–6 h in wild-type mice without any lethality. In contrast, treatment of Sod1−/− or Gpx1−/− mice with a similar concentration of diquat resulted in a significant increase in oxidative damage within an hour of treatment and was lethal, i.e., these mice are extremely sensitive to the oxidative stress generated by diquat. The expression response to elevated oxidative stress in vivo does not involve an upregulation of classic antioxidant genes, although long-term oxidative stress in Sod1−/− mice leads to a significant upregulation of thiol antioxidants (e.g., Mt1, Srxn1, Gclc, Txnrd1), which appears to be mediated by the redox-sensitive transcription factor Nrf2. The main finding of our study is that the common response to elevated oxidative stress with diquat treatment in wild-type, Gpx1−/−, and Sod1−/− mice and in untreated Sod1−/− mice is an upregulation of p53 target genes ( p21, Gdf15, Plk3, Atf3, Trp53inp1, Ddit4, Gadd45a, Btg2, Ndrg1). A retrospective comparison with previous studies shows that induction of these p53 target genes is a conserved expression response to oxidative stress, in vivo and in vitro, in different species and different cells/organs.

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Jiang, Wenqiang, Lei Yang, Yiqin He, Haotian Zhang, Wei Li, Huaigu Chen, Dongfang Ma, and Junliang Yin. "Genome-wide identification and transcriptional expression analysis of superoxide dismutase (SOD) family in wheat (Triticum aestivum)." PeerJ 7 (November 19, 2019): e8062. http://dx.doi.org/10.7717/peerj.8062.

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Superoxide dismutases (SODs) are a family of key antioxidant enzymes that play a crucial role in plant growth and development. Previously, this gene family has been investigated in Arabidopsis and rice. In the present study, a genome-wide analysis of the SOD gene family in wheat were performed. Twenty-six SOD genes were identified from the whole genome of wheat, including 17 Cu/Zn-SODs, six Fe-SODs, and three Mn-SODs. The chromosomal location mapping analysis indicated that these three types of SOD genes were only distributed on 2, 4, and 7 chromosomes, respectively. Phylogenetic analyses of wheat SODs and several other species revealed that these SOD proteins can be assigned to two major categories. SOD1 mainly comprises of Cu/Zn-SODs, and SOD2 mainly comprises of Fe-SODs and Mn-SODs. Gene structure and motif analyses indicated that most of the SOD genes showed a relatively conserved exon/intron arrangement and motif composition. Analyses of transcriptional data indicated that most of the wheat SOD genes were expressed in almost all of the examined tissues and had important functions in abiotic stress resistance. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to reveal the regulating roles of wheat SOD gene family in response to NaCl, mannitol, and polyethylene glycol stresses. qRT-PCR showed that eight randomly selected genes with relatively high expression levels responded to all three stresses based on released transcriptome data. However, their degree of response and response patterns were different. Interestingly, among these genes, TaSOD1.7, TaSOD1.9, TaSOD2.1, and TaSOD2.3 feature research value owing to their remarkable expression-fold change in leaves or roots under different stresses. Overall, our results provide a basis of further functional research on the SOD gene family in wheat and facilitate their potential use for applications in the genetic improvement on wheat in drought and salt stress environments.

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Bernard, Emilien, Antoine Pegat, Juliette Svahn, Françoise Bouhour, Pascal Leblanc, Stéphanie Millecamps, Stéphane Thobois, Claire Guissart, Serge Lumbroso, and Kevin Mouzat. "Clinical and Molecular Landscape of ALS Patients with SOD1 Mutations: Novel Pathogenic Variants and Novel Phenotypes. A Single ALS Center Study." International Journal of Molecular Sciences 21, no. 18 (September 16, 2020): 6807. http://dx.doi.org/10.3390/ijms21186807.

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Mutations in the copper zinc superoxide dismutase 1 (SOD1) gene are the second most frequent cause of familial amyotrophic lateral sclerosis (ALS). Nearly 200 mutations of this gene have been described so far. We report all SOD1 pathogenic variants identified in patients followed in the single ALS center of Lyon, France, between 2010 and 2020. Twelve patients from 11 unrelated families are described, including two families with the not yet described H81Y and D126N mutations. Splice site mutations were detected in two families. We discuss implications concerning genetic screening of SOD1 gene in familial and sporadic ALS.

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Furukawa, Yoshiaki. "Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral Sclerosis." Neurology Research International 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/323261.

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Dominant mutations in a Cu, Zn-superoxide dismutase (SOD1) gene cause a familial form of amyotrophic lateral sclerosis (ALS). While it remains controversial how SOD1 mutations lead to onset and progression of the disease, manyin vitroandin vivostudies have supported a gain-of-toxicity mechanism where pathogenic mutations contribute to destabilizing a native structure of SOD1 and thus facilitate misfolding and aggregation. Indeed, abnormal accumulation of SOD1-positive inclusions in spinal motor neurons is a pathological hallmark in SOD1-related familial ALS. Furthermore, similarities in clinical phenotypes and neuropathology of ALS cases with and without mutations insod1gene have implied a disease mechanism involving SOD1 common to all ALS cases. Although pathogenic roles of wild-type SOD1 in sporadic ALS remain controversial, recent developments of novel SOD1 antibodies have made it possible to characterize wild-type SOD1 under pathological conditions of ALS. Here, I have briefly reviewed recent progress on biochemical and immunohistochemical characterization of wild-type SOD1 in sporadic ALS cases and discussed possible involvement of wild-type SOD1 in a pathomechanism of ALS.

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Popović, Nataša, Vesna Stojiljković, Snežana Pejić, Ana Todorović, Ivan Pavlović, Ljubica Gavrilović, and Snežana B. Pajović. "Modulation of Hippocampal Antioxidant Defense System in Chronically Stressed Rats by Lithium." Oxidative Medicine and Cellular Longevity 2019 (February 17, 2019): 1–11. http://dx.doi.org/10.1155/2019/8745376.

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This study examined the effects of lithium on gene expression and activity of the antioxidant enzymes copper zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in the hippocampus of chronically stressed rats. In addition, we examined the effects of lithium on anxiety behaviors, hippocampal concentrations of dopamine (DA) and malondialdehyde (MDA), protein levels of brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT), as well as activity of monoamine oxidase (MAO) in chronically stressed rats. The investigated parameters were quantified by real-time RT-PCR, Western blot analyses, and assays of enzyme activities. We found that lithium did not change gene expression of SOD1, CAT, GPx, and GR but decreased gene expression of SOD2 in chronically stressed rats. A very important result in this study was that lithium treatment decreased the enzyme activities of SOD1 and SOD2 but increased the enzyme activities of GPx and GR in stress condition, which indicates the control of redox balance. The reduced concentration of MDA confirms this. In addition, we found that lithium treatment decreased high protein levels of BDNF and DAT in chronically stressed rats to the level found in unstressed animals. Also, lithium treatment increased the expression of TH but decreased the enzyme activity of MAO B, which contributed to the increase of hippocampal concentration of DA in chronically stressed rats to the level of unstressed animals. Finally, lithium treatment in animals exposed to chronic stress increased the time spent in open arms. Lithium-induced modulation of hippocampal antioxidant status and attenuation of oxidative stress stabilized behavior in animals with high anxiety index. In addition, reduced oxidative stress was followed by the changes of both turnover of DA and levels of BDNF protein in chronically stressed rats treated with lithium. These findings may be important in preclinical research of the effects of lithium on oxidative stress level in pathological conditions.

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Castillo-Martín, Miriam, Marc Yeste, Eva Pericuesta, Roser Morató, Alfonso Gutiérrez-Adán, and Sergi Bonet. "Effects of vitrification on the expression of pluripotency, apoptotic and stress genes in in vitro-produced porcine blastocysts." Reproduction, Fertility and Development 27, no. 7 (2015): 1072. http://dx.doi.org/10.1071/rd13405.

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The aims of the present study were to: (1) evaluate the effect of vitrification and warming on quality parameters and expression levels of pluripotency, apoptotic and stress genes in in vitro-produced (IVP) porcine blastocysts; and (ii) determine the correlation between these parameters. To this end, total cell number, DNA fragmentation, peroxide levels and the relative transcript abundance of BCL-2 associated X protein (BAX), BCL2-like 1 (BCL2L1), heat shock protein 70 (HSPA1A), POU class 5 homeobox 1 (POU5F1), superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) were analysed in fresh and vitrified IVP blastocysts. The results suggest that vitrification procedures have no effect on total cell number and gene expression of BAX, BCL2L1, SOD1 and SOD2 or the BAX : BCL2L1 ratio. Nevertheless, a significant increase in DNA fragmentation (2.9 ± 0.4% vs 11.9 ± 2.0%) and peroxide levels (80.4 ± 2.6 vs 97.2 ± 3.1) were seen in vitrified compared with Day 7 fresh blastocysts. In addition, after blastocyst vitrification, relative transcript abundance was downregulated for POU5F1 and upregulated for HSPA1A. Finally, there was a significant correlation of POU5F1 and HSPA1A with DNA fragmentation (POU5F1, r = –0.561; HSPA1A, r = 0.604) and peroxide levels (POU5F1, r = –0.590; HSPA1A, r = 0.621). In conclusion, under the conditions of the present study, vitrification and warming of IVP porcine blastocysts resulted in altered expression of POU5F1 and HSPA1A, but had no effect on BAX, BCL2L1, SOD1 and SOD2 expression.

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Valderas, Michelle Wright, and Mark E. Hart. "Identification and Characterization of a Second Superoxide Dismutase Gene (sodM) fromStaphylococcus aureus." Journal of Bacteriology 183, no. 11 (June 1, 2001): 3399–407. http://dx.doi.org/10.1128/jb.183.11.3399-3407.2001.

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ABSTRACT A gene encoding superoxide dismutase (SOD), sodM, fromS. aureus was cloned and characterized. The deduced amino acid sequence specifies a 187-amino-acid protein with 75% identity to the S. aureus SodA protein. Amino acid sequence comparisons with known SODs and relative insensitivity to hydrogen peroxide and potassium cyanide indicate that SodM most likely uses manganese (Mn) as a cofactor. The sodM gene expressed from a plasmid rescued an Escherichia coli double mutant (sodA sodB) under conditions that are otherwise lethal. SOD activity gels ofS. aureus RN6390 whole-cell lysates revealed three closely migrating bands of activity. The two upper bands were absent in asodM mutant, while the two lower bands were absent in asodA mutant. Thus, the middle band of activity most likely represents a SodM-SodA hybrid protein. All three bands of activity increased as highly aerated cultures entered the late exponential phase of growth, SodM more so than SodA. Viability of the sodAand sodM sodA mutants but not the sodM mutant was drastically reduced under oxidative stress conditions generated by methyl viologen (MV) added during the early exponential phase of growth. However, only the viability of the sodM sodA mutant was reduced when MV was added during the late exponential and stationary phases of growth. These data indicate that while SodA may be the major SOD activity in S. aureus throughout all stages of growth, SodM, under oxidative stress, becomes a major source of activity during the late exponential and stationary phases of growth such that viability and growth of an S. aureus sodA mutant are maintained.

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Gusti, Amani M. T., Safaa Y. Qusti, Eida M. Alshammari, Eman A. Toraih, and Manal S. Fawzy. "Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study." Antioxidants 10, no. 4 (April 13, 2021): 595. http://dx.doi.org/10.3390/antiox10040595.

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Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), and homozygote and recessive models for GPX1 rs1800668 (A/G). In contrast, SOD3 rs2536512 (A/G) were less likely to be obese under heterozygote and dominant models. The CGAG, CAAA, TGGG, and CGAG combined genotypes showed a higher risk of obesity. In conclusion, the present results suggest that oxidative-stress-related genetic determinants could significantly associate with obesity risk in the study population.

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Farooq, Umer, Yanjun Pan, Yanfei Lin, Ying Wang, Hiroyuki Osada, Lan Xiang, and Jianhua Qi. "Structure Characterization and Action Mechanism of an Antiaging New Compound from Gastrodia elata Blume." Oxidative Medicine and Cellular Longevity 2019 (May 6, 2019): 1–10. http://dx.doi.org/10.1155/2019/5459862.

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A new compound, bis(4-hydroxybenzyl)ether mono-β-L-galactopyranoside (1), was isolated from the rhizome of Gastrodia elata Blume. Its structure was elucidated using extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-TOF-MS, and chemical derivatization. Compound 1 extended the replicative lifespan of K6001 and the chronological lifespan of YOM36 yeast strains. To understand the mechanism of action, oxidative stress assessment, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, catalase (CAT) and total glutathione peroxidase (GPx) activity assays, and replicative lifespan assay of sod1, sod2, uth1, and skn7 yeast mutant strains were performed. Results indicated the significant increase in the survival rate of yeast under oxidative stress after treatment with 1. ROS and MDA levels were reduced significantly. Meanwhile, the activity of CAT and GPx was significantly increased. The lifespan of sod1, sod2, uth1, and skn7 mutants of K6001 was not affected by 1. Furthermore, we investigated the gene expression related to longevity after administrating 1. The significant increase of Sir2 and reduction of Uth1 gene expression in the 1-treated group were observed. These results indicated that antioxidative stress played an important role in the antiaging effect of 1; Sir2 and Uth1 genes were involved in antiaging effects of 1.

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Couillard-Després, Sébastien, Qinzhang Zhu, Philip C. Wong, Donald L. Price, Don W. Cleveland, and Jean-Pierre Julien. "Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase." Proceedings of the National Academy of Sciences 95, no. 16 (August 4, 1998): 9626–30. http://dx.doi.org/10.1073/pnas.95.16.9626.

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To investigate the role of neurofilaments in motor neuron disease caused by superoxide dismutase (SOD1) mutations, transgenic mice expressing a amyotrophic lateral sclerosis-linked SOD1 mutant (SOD1G37R) were mated with transgenic mice expressing human neurofilament heavy (NF-H) subunits. Unexpectedly, expression of human NF-H transgenes increased by up to 65%, the mean lifespan of SOD1G37R mice. Microscopic examination corroborated the protective effect of NF-H protein against SOD1 toxicity. Although massive neurodegeneration occurred in 1-yr-old mice expressing SOD1G37R alone, spinal root axons and motor neurons were remarkably spared in doubly SOD1G37R;NF-H-transgenic littermates.

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Fontagné, Stéphanie, Emilie Lataillade, Janine Brèque, and Sadasivam Kaushik. "Lipid peroxidative stress and antioxidant defence status during ontogeny of rainbow trout (Oncorhynchus mykiss)." British Journal of Nutrition 100, no. 1 (July 2008): 102–11. http://dx.doi.org/10.1017/s0007114507876215.

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The objective of the present study was to characterise some important antioxidant enzymes and their relationships with retinoids and lipid peroxidation during rainbow trout (Oncorhynchus mykiss) early development. Eggs were incubated at 7°C until the swim-up stage whereupon fry were fed two semi-purified diets with 0 % (CO) and 8 % (OX) oxidised lipid respectively for 2 months at 17°C. The activities and gene expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were determined as well as the levels of retinoids, F2-isoprostanes and lipid-soluble fluorescent products (LSFP) at various developmental stages. Only SOD had a detectable activity in embryos which increased during development and was linked with an increase of mitochondrial (SOD2) and cytosolic (SOD1) gene expression. SOD1 and SOD2 mRNA were more abundant in fry fed OX than in fry fed CO. CAT activity and gene expression also increased during development and were higher in fry fed OX compared with fry fed CO. Activity of Se-dependent GPX (Se-GPX) increased during development. The gene expression of cytosolic Se-GPX (GPX1) increased from hatching to 2-month-fed fry. Both phospholipid-hydroperoxide GPX and GPX1 genes were more expressed in fry fed OX than in fry fed CO. Retinoids decreased during development and, by 2 months, were lowered in fry fed OX compared with those fed CO. The levels of LSFP were higher in fry fed OX compared with fry fed CO. The present study demonstrates that antioxidant defence systems are active all through the development of rainbow trout and modulated by feeding oxidised lipid.

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Chen, Ling‐Chun, Andrew P. Smith, Yong Ben, Belma Zukic, Sheila Ignacio, Dan Moore, and Nancy M. Lee. "Temporal gene expression patterns in G93A/SOD1 mouse." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 5, no. 3 (September 2004): 164–71. http://dx.doi.org/10.1080/14660820410017091.

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Pytte, Julia, Loren L. Flynn, Ryan S. Anderton, Frank L. Mastaglia, Frances Theunissen, Ian James, Abigail Pfaff, et al. "Disease-modifying effects of an SCAF4 structural variant in a predominantly SOD1 ALS cohort." Neurology Genetics 6, no. 4 (July 1, 2020): e470. http://dx.doi.org/10.1212/nxg.0000000000000470.

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ObjectiveTo test the hypothesis that rs573116164 will have disease-modifying effects in patients with superoxide dismutase 1 (SOD1) familial amyotrophic lateral sclerosis (fALS), we characterized rs573116164 within a cohort of 190 patients with fALS and 560 healthy age-matched controls to assess the variant for association with various measures of disease.MethodsUsing a previously described bioinformatics evaluation algorithm, a polymorphic short structural variant associated with SOD1 was identified according to its theoretical effect on gene expression. An 12–18 poly-T repeat (rs573116164) within the 3′ untranslated region of serine and arginine rich proteins-related carboxy terminal domain associated factor 4 (SCAF4), a gene that is adjacent to SOD1, was assessed for disease association and influence on survival and age at onset in an fALS cohort using PCR, Sanger sequencing, and capillary separation techniques for allele detection.ResultsIn a North American cohort of predominantly SOD1 fALS patients (n =190) and age-matched healthy controls (n = 560), we showed that carriage of an 18T SCAF4 allele was associated with disease within this cohort (odds ratio [OR] 6.6; 95% confidence interval [CI] 3.9–11.2; p = 4.0e-11), but also within non-SOD1 cases (n = 27; OR 5.3; 95% CI 1.9–14.5; p = 0.0014). This finding suggests genetically SOD1-independent effects of SCAF4 on fALS susceptibility. Furthermore, carriage of an 18T allele was associated with a 26-month reduction in survival time (95% CI 6.6–40.8; p = 0.014), but did not affect age at onset of disease.ConclusionsThe findings in this fALS cohort suggest that rs573116164 could have SOD1-independent and broader relevance in ALS, warranting further investigation in other fALS and sporadic ALS cohorts, as well as studies of functional effects of the 18T variant on gene expression.

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Semmler, Sabrina, Myriam Gagné, Pranav Garg, Sarah R. Pickles, Charlotte Baudouin, Emeline Hamon-Keromen, Laurie Destroismaisons, et al. "TNF receptor–associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation." Journal of Biological Chemistry 295, no. 12 (February 6, 2020): 3808–25. http://dx.doi.org/10.1074/jbc.ra119.011215.

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Amyotrophic lateral sclerosis (ALS) is a fatal disease, characterized by the selective loss of motor neurons leading to paralysis. Mutations in the gene encoding superoxide dismutase 1 (SOD1) are the second most common cause of familial ALS, and considerable evidence suggests that these mutations result in an increase in toxicity due to protein misfolding. We previously demonstrated in the SOD1G93A rat model that misfolded SOD1 exists as distinct conformers and forms deposits on mitochondrial subpopulations. Here, using SOD1G93A rats and conformation-restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the interactomes of the mitochondrial pools of misfolded SOD1. This strategy identified binding proteins that uniquely interacted with either AMF7-63 or B8H10-reactive SOD1 conformers as well as a high proportion of interactors common to both conformers. Of this latter set, we identified the E3 ubiquitin ligase TNF receptor–associated factor 6 (TRAF6) as a SOD1 interactor, and we determined that exposure of the SOD1 functional loops facilitates this interaction. Of note, this conformational change was not universally fulfilled by all SOD1 variants and differentiated TRAF6 interacting from TRAF6 noninteracting SOD1 variants. Functionally, TRAF6 stimulated polyubiquitination and aggregation of the interacting SOD1 variants. TRAF6 E3 ubiquitin ligase activity was required for the former but was dispensable for the latter, indicating that TRAF6-mediated polyubiquitination and aggregation of the SOD1 variants are independent events. We propose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology of ALS.

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Maier, Marcel, Tobias Welt, Fabian Wirth, Fabio Montrasio, Daniel Preisig, Jordan McAfoose, Fernando G. Vieira, et al. "A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis." Science Translational Medicine 10, no. 470 (December 5, 2018): eaah3924. http://dx.doi.org/10.1126/scitranslmed.aah3924.

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Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 and cause familial amyotrophic lateral sclerosis (FALS). However, the implications of wild-type SOD1 misfolding in sporadic forms of ALS (SALS) remain unclear. By screening human memory B cells from a large cohort of healthy elderly subjects, we generated a recombinant human monoclonal antibody (α-miSOD1) that selectively bound to misfolded SOD1, but not to physiological SOD1 dimers. On postmortem spinal cord sections from 121 patients with ALS, α-miSOD1 antibody identified misfolded SOD1 in a majority of cases, regardless of their SOD1 genotype. In contrast, the α-miSOD1 antibody did not bind to its epitope in most of the 41 postmortem spinal cord sections from non-neurological control (NNC) patients. In transgenic mice overexpressing disease-causing human SOD1G37R or SOD1G93A mutations, treatment with the α-miSOD1 antibody delayed the onset of motor symptoms, extended survival by up to 2 months, and reduced aggregation of misfolded SOD1 and motor neuron degeneration. These effects were obtained whether α-miSOD1 antibody treatment was administered by direct brain infusion or peripheral administration. These results support the further development of α-miSOD1 antibody as a candidate treatment for ALS involving misfolding of SOD1.

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Niwa, Jun-ichi, Shin-ichi Yamada, Shinsuke Ishigaki, Jun Sone, Miho Takahashi, Masahisa Katsuno, Fumiaki Tanaka, Manabu Doyu, and Gen Sobue. "Disulfide Bond Mediates Aggregation, Toxicity, and Ubiquitylation of Familial Amyotrophic Lateral Sclerosis-linked Mutant SOD1." Journal of Biological Chemistry 282, no. 38 (July 31, 2007): 28087–95. http://dx.doi.org/10.1074/jbc.m704465200.

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Mutations in the Cu/Zn-superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS) through the gain of a toxic function; however, the nature of this toxic function remains largely unknown. Ubiquitylated aggregates of mutant SOD1 proteins in affected brain lesions are pathological hallmarks of the disease and are suggested to be involved in several proposed mechanisms of motor neuron death. Recent studies suggest that mutant SOD1 readily forms an incorrect disulfide bond upon mild oxidative stress in vitro, and the insoluble SOD1 aggregates in spinal cord of ALS model mice contain multimers cross-linked via intermolecular disulfide bonds. Here we show that a non-physiological intermolecular disulfide bond between cysteines at positions 6 and 111 of mutant SOD1 is important for high molecular weight aggregate formation, ubiquitylation, and neurotoxicity, all of which were dramatically reduced when the pertinent cysteines were replaced in mutant SOD1 expressed in Neuro-2a cells. Dorfin is a ubiquityl ligase that specifically binds familial ALS-linked mutant SOD1 and ubiquitylates it, thereby promoting its degradation. We found that Dorfin ubiquitylated mutant SOD1 by recognizing the Cys6- and Cys111-disulfide cross-linked form and targeted it for proteasomal degradation.

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Lobsiger, Christian S., Séverine Boillée, and Don W. Cleveland. "Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons." Proceedings of the National Academy of Sciences 104, no. 18 (April 26, 2007): 7319–26. http://dx.doi.org/10.1073/pnas.0702230104.

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Global, age-dependent changes in gene expression from rodent models of inherited ALS caused by dominant mutations in superoxide-dismutase 1 (SOD1) were identified by using gene arrays and RNAs isolated from purified embryonic and adult motor neurons. Comparison of embryonic motor neurons expressing a dismutase active ALS-linked mutant SOD1 with those expressing comparable levels of wild-type SOD1 revealed the absence of mutant-induced mRNA changes. An age-dependent mRNA change that developed presymptomatically in adult motor neurons collected by laser microdissection from mice expressing dismutase active ALS-linked mutants was dysregulation of the d/l-serine biosynthetic pathway, previously linked to both excitotoxic and neurotrophic effects. An unexpected dysregulation common to motor neurons expressing either dismutase active or inactive mutants was induction of neuronally derived components of the classic complement system and the regenerative/injury response. Alteration of these mutant SOD1-induced pathways identified a set of targets for therapies for inherited ALS.

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Iuchi, Yoshihito, Futoshi Okada, Rina Takamiya, Noriko Kibe, Satoshi Tsunoda, Osamu Nakajima, Kazuyo Toyoda, et al. "Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes." Biochemical Journal 422, no. 2 (August 13, 2009): 313–20. http://dx.doi.org/10.1042/bj20090176.

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Oxidative stress has been implicated as a cause of various diseases such as anaemia. We found that the SOD1 [Cu,Zn-SOD (superoxide dismutase)] gene deficiency causes anaemia, the production of autoantibodies against RBCs (red blood cells) and renal damage. In the present study, to further understand the role of oxidative stress in the autoimmune response triggered by SOD1 deficiency, we generated mice that had the hSOD1 (human SOD1) transgene under regulation of the GATA-1 promoter, and bred the transgene onto the SOD1−/− background (SOD1−/−;hSOD1tg/+). The lifespan of RBCs, levels of intracellular reactive oxygen species, and RBC content in SOD1−/−;hSOD1tg/+ mice, were approximately equivalent to those of SOD1+/+ mice. The production of antibodies against lipid peroxidation products, 4-hydroxy-2-nonenal and acrolein, as well as autoantibodies against RBCs and carbonic anhydrase II were elevated in the SOD1−/− mice, but were suppressed in the SOD1−/−;hSOD1tg/+ mice. Renal function, as judged by blood urea nitrogen, was improved in the transgenic mice. These results rule out the involvement of a defective immune system in the autoimmune response of SOD1-deficient mice, because SOD1−/−;hSOD1tg/+ mice carry the hSOD1 protein only in RBCs. Metabolomic analysis indicated a shift in glucose metabolism to the pentose phosphate pathway and a decrease in the energy charge potential of RBCs in SOD1-deficient mice. We conclude that the increase in reactive oxygen species due to SOD1 deficiency accelerates RBC destruction by affecting carbon metabolism and increasing oxidative modification of lipids and proteins. The resulting oxidation products are antigenic and, consequently, trigger autoantibody production, leading to autoimmune responses.

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Kim, Jung, Hyeong Kim, and Chang Son. "Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model." International Journal of Molecular Sciences 19, no. 10 (October 15, 2018): 3174. http://dx.doi.org/10.3390/ijms19103174.

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Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes including aging. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability especially to age-related and chronic diseases. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions. Microarray analysis results, which were consistent with quantitative polymerase chain reaction (qPCR) results, showed that catalase, Gpx3, and Gpx4 were most highly regulated in the liver, kidney, and testes. We also found the tissue-specific gene expression of SOD1 (liver and kidney), SOD2 (heart and muscle), and SOD3 (lung and kidney). The current results will serve as a reference for animal models and help advance our understanding of tissue-specific variability in oxidative stress-associated pathogenesis.

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Wigner, Paulina, Ewelina Synowiec, Paweł Jóźwiak, Piotr Czarny, Michał Bijak, Gabriela Barszczewska, Katarzyna Białek, et al. "The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine." Genes 11, no. 6 (June 11, 2020): 644. http://dx.doi.org/10.3390/genes11060644.

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Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

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CHANG, Mun Seog, Hae Yong YOO, and Hyune Mo RHO. "Positive and negative regulatory elements in the upstream region of the rat Cu/Zn-superoxide dismutase gene." Biochemical Journal 339, no. 2 (April 8, 1999): 335–41. http://dx.doi.org/10.1042/bj3390335.

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Cu/Zn-superoxide dismutase (SOD1) catalyses the dismutation of superoxide radicals and neutralizes the oxidative effects of various chemicals. Deletion analysis of the upstream region of the rat SOD1 gene revealed that the promoter contains a positive regulatory element (PRE) and a negative regulatory element (NRE), which encompass the regions from -576 to -412 and from -412 to -305 respectively from the site of initiation of transcription. These DNA elements showed enhancer and silencer activities respectively in the natural context and in a heterologous promoter system. Using an electrophoretic-mobility-shift assay and a supershift assay with a specific antibody, the cis-elements of the PRE and NRE were identified as binding sites for transcription factors Elk1 and YY1 (Ying-Yang 1) respectively. Consistent with the presumed roles of the PRE and NRE, Elk1 increased SOD1 gene transcription about 4–5-fold, whereas YY1 exerted a negative effect of about 6-fold. Mutations of the Elk1- and YY1-binding sites led to diminution and elevation respectively of transcriptional activities, both in the natural context and in heterologous promoter systems. These results suggest that the transcription factors Elk1 and YY1, binding in the PRE and NRE respectively, co-ordinate the expression of the SOD1 gene.

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Proctor, Elizabeth A., Lanette Fee, Yazhong Tao, Rachel L. Redler, James M. Fay, Yuliang Zhang, Zhengjian Lv, et al. "Nonnative SOD1 trimer is toxic to motor neurons in a model of amyotrophic lateral sclerosis." Proceedings of the National Academy of Sciences 113, no. 3 (December 30, 2015): 614–19. http://dx.doi.org/10.1073/pnas.1516725113.

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Since the linking of mutations in the Cu,Zn superoxide dismutase gene (sod1) to amyotrophic lateral sclerosis (ALS) in 1993, researchers have sought the connection between SOD1 and motor neuron death. Disease-linked mutations tend to destabilize the native dimeric structure of SOD1, and plaques containing misfolded and aggregated SOD1 have been found in the motor neurons of patients with ALS. Despite advances in understanding of ALS disease progression and SOD1 folding and stability, cytotoxic species and mechanisms remain unknown, greatly impeding the search for and design of therapeutic interventions. Here, we definitively link cytotoxicity associated with SOD1 aggregation in ALS to a nonnative trimeric SOD1 species. We develop methodology for the incorporation of low-resolution experimental data into simulations toward the structural modeling of metastable, multidomain aggregation intermediates. We apply this methodology to derive the structure of a SOD1 trimer, which we validate in vitro and in hybridized motor neurons. We show that SOD1 mutants designed to promote trimerization increase cell death. Further, we demonstrate that the cytotoxicity of the designed mutants correlates with trimer stability, providing a direct link between the presence of misfolded oligomers and neuron death. Identification of cytotoxic species is the first and critical step in elucidating the molecular etiology of ALS, and the ability to manipulate formation of these species will provide an avenue for the development of future therapeutic strategies.

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Lastres-Becker, Isabel, Gracia Porras, Marina Arribas-Blázquez, Inés Maestro, Daniel Borrego-Hernández, Patricia Boya, Sebastián Cerdán, Alberto García-Redondo, Ana Martínez, and Ángeles Martin-Requero. "Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy." International Journal of Molecular Sciences 22, no. 6 (March 16, 2021): 3007. http://dx.doi.org/10.3390/ijms22063007.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily transmitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mitochondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.

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Côrtes, Cristiano, Marie-France Palin, Nathalie Gagnon, Chaouki Benchaar, Pierre Lacasse, and Hélène V. Petit. "Mammary gene expression and activity of antioxidant enzymes and concentration of the mammalian lignan enterolactone in milk and plasma of dairy cows fed flax lignans and infused with flax oil in the abomasum." British Journal of Nutrition 108, no. 8 (January 3, 2012): 1390–98. http://dx.doi.org/10.1017/s0007114511006829.

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The objectives of the study were to investigate the effects of dietary supplementation of flax hulls and/or flax oil on the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)) in plasma and the mammary gland and the relative mRNA abundance of antioxidant genes in the mammary gland of dairy cows. A total of eight dairy cows were used in a replicated 4 × 4 Latin square design. There were four treatments: control with no flax hulls (CONT), 9·88 % flax hulls in the DM (HULL), control with 500 g flax oil/d infused in the abomasum (COFO), 9·88 % flax hulls in the DM and 500 g flax oil/d infused in the abomasum (HUFO). Plasma GPX activity tended to decrease with flax oil supplementation. Cows fed HULL had higher levels of CAT, GPX1 and SOD1 mRNA in the mammary gland and lower mRNA abundance of GPX3, SOD2 and SOD3 compared with those fed CONT. Abundance of CAT, GPX1, GPX3, SOD2 and SOD3 mRNA was down-regulated in the mammary gland of cows fed HUFO compared to those fed CONT. The mRNA abundance of CAT, GPX1, GPX3 and SOD3 was lower in the mammary gland of cows fed COFO than in the mammary gland of cows fed CONT. The present study demonstrates that flax hulls contribute to increasing the abundance of some antioxidant genes, which can contribute to protecting against oxidative stress damage occurring in the mammary gland and other tissues of dairy cows.

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40

Bastow, Emma L., Campbell W. Gourlay, and Mick F. Tuite. "Using yeast models to probe the molecular basis of amyotrophic lateral sclerosis." Biochemical Society Transactions 39, no. 5 (September 21, 2011): 1482–87. http://dx.doi.org/10.1042/bst0391482.

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ALS (amyotrophic lateral sclerosis) is a fatal neurodegenerative disease attributable to the death of motor neurons. Associated with ALS are mutations in the genes encoding SOD1 (superoxide dismutase 1), FUS (fused in Sarcoma) protein and TDP-43 (TAR DNA-binding protein-43) each of which leads to aggregation of the respective protein. For example, the ALS-associated mutations in the hSOD1 (human SOD1) gene typically destabilize the native SOD homodimer, leading to misfolding, aggregation and degradation of SOD1. The ALS-associated pathology is not a consequence of the functional inactivation of SOD1 itself, but is rather due to a toxic gain-of-function triggered by mutant SOD1. Recently, the molecular basis of a number of human neurodegenerative diseases resulting from protein misfolding and aggregation, including fALS (familial ALS), was probed by using the baker's yeast, Saccharomyces cerevisiae, as a highly tractable model. Such studies have, for example, identified novel mutant SOD1-specific interactions and demonstrated that mutant SOD1 disrupts mitochondrial homoeostasis. Features of ALS associated with TDP-43 aggregation have also been recapitulated in S. cerevisiae including the identification of modulators of the toxicity of TDP-43. In this paper, we review recent studies of ALS pathogenesis using S. cerevisiae as a model organism and summarize the potential mechanisms involved in ALS progression.

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41

Dacanay, A., S. C. Johnson, R. Bjornsdottir, R. O. Ebanks, N. W. Ross, M. Reith, R. K. Singh, J. Hiu, and L. L. Brown. "Molecular Characterization and Quantitative Analysis of Superoxide Dismutases in Virulent and Avirulent Strains of Aeromonas salmonicida subsp. salmonicida." Journal of Bacteriology 185, no. 15 (August 1, 2003): 4336–44. http://dx.doi.org/10.1128/jb.185.15.4336-4344.2003.

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ABSTRACT Aeromonas salmonicida subsp. salmonicida is a facultatively intracellular gram-negative bacterium that is the etiological agent of furunculosis, a bacterial septicemia of salmonids that causes significant economic loss to the salmon farming industry. The mechanisms by which A. salmonicida evades intracellular killing may be relevant in understanding virulence and the eventual design of appropriate treatment strategies for furunculosis. We have identified two open reading frames (ORFs) and related upstream sequences that code for two putative superoxide dismutases (SODs), sodA and sodB. The sodA gene encoded a protein of 204 amino acids with a molecular mass of approximately 23.0 kDa (SodA) that had high similarity to other prokaryotic Mn-SODs. The sodB gene encoded a protein of 194 amino acids with a molecular mass of approximately 22.3 kDa that had high similarity to other prokaryotic Fe-SODs. Two enzymes with activities consistent with both these ORFs were identified by inhibition of O2 −-catalyzed tetrazolium salt reduction in both gels and microtiter plate assays. The two enzymes differed in their expression patterns in in vivo- and in vitro-cultured bacteria. The regulatory sequences upstream of putative sodA were consistent with these differences. We could not identify other SOD isozymes such as sodC either functionally or through data mining. Levels of SOD were significantly higher in virulent than in avirulent strains of A. salmonicida subsp. salmonicida strain A449 when cultured in vitro and in vivo.

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Sábado, Javier, Anna Casanovas, Olga Tarabal, Marta Hereu, Lídia Piedrafita, Jordi Calderó, and Josep E. Esquerda. "Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis." BioMed Research International 2014 (2014): 1–13. http://dx.doi.org/10.1155/2014/852163.

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Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations ofsuperoxide dismutase 1(SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used theSOD1G93Amouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

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Trist, Benjamin G., Jennifer A. Fifita, Sarah E. Freckleton, Dominic J. Hare, Simon J. G. Lewis, Glenda M. Halliday, Ian P. Blair, and Kay L. Double. "Accumulation of dysfunctional SOD1 protein in Parkinson’s disease is not associated with mutations in the SOD1 gene." Acta Neuropathologica 135, no. 1 (October 19, 2017): 155–56. http://dx.doi.org/10.1007/s00401-017-1779-6.

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Tak, Yeong Jin, Ju-Hwang Park, Hyangshuk Rhim, and Seongman Kang. "ALS-Related Mutant SOD1 Aggregates Interfere with Mitophagy by Sequestering the Autophagy Receptor Optineurin." International Journal of Molecular Sciences 21, no. 20 (October 13, 2020): 7525. http://dx.doi.org/10.3390/ijms21207525.

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive demise of motor neurons. One of the causes of familial ALS is the mutation of the gene encoding superoxide dismutase 1 (SOD1), which leads to abnormal protein aggregates. How SOD1 aggregation drives ALS is still poorly understood. Recently, ALS pathogenesis has been functionally implicated in mitophagy, specifically the clearance of damaged mitochondria. Here, to understand this mechanism, we investigated the relationship between the mitophagy receptor optineurin and SOD1 aggregates. We found that mutant SOD1 (mSOD1) proteins associate with and then sequester optineurin, which is required to form the mitophagosomes, to aggregates in N2a cells. Optineurin recruitment into mSOD1 aggregates resulted in a reduced mitophagy flux. Furthermore, we observed that an exogenous augmentation of optineurin alleviated the cellular cytotoxicity induced by mSOD1. Taken together, these studies demonstrate that ALS-linked mutations in SOD1 interfere with the mitophagy process through optineurin sequestration, suggesting that the accumulation of damaged mitochondria may play a crucial role in the pathophysiological mechanisms contributing to ALS.

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Saito, Atsushi, Takeshi Hayashi, Shuzo Okuno, Tatsuro Nishi, and Pak H. Chan. "Modulation of p53 Degradation via MDM2-Mediated Ubiquitylation and the Ubiquitin–Proteasome System during Reperfusion after Stroke: Role of Oxidative Stress." Journal of Cerebral Blood Flow & Metabolism 25, no. 2 (February 2005): 267–80. http://dx.doi.org/10.1038/sj.jcbfm.9600028.

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The tumor suppressor gene p53 plays an important role in the regulation of apoptosis through transcriptional activation of cell cycle control. Degradation of p53 hinders its role in apoptosis regulation. Recent studies have shown that MDM2-mediated ubiquitylation and the ubiquitin–proteasome system are critical regulating systems of p53 ubiquitylation. However, the mechanism regulating p53-mediated neuronal apoptosis after cerebral ischemia remains unknown. We examined the MDM2 pathway and the ubiquitin–proteasome system using a transient focal cerebral ischemia (tFCI) model and analyzed the interaction between p53 regulation and superoxide using copper/zinc superoxide dismutase (SOD1) transgenic mice after tFCI. p53 degradation and ubiquitylation were detected after tFCI. The accumulation of ubiquitylated p53 was inhibited and p53 degradation was facilitated by SOD1. Nuclear translocation and MDM2/Akt interaction were detected after tFCI and were inhibited by phosphatidylinositol 3-kinase inhibition and promoted by SOD1. Cytosolic translocation of the p53/MDM2 complex was detected after tFCI and was promoted by SOD1. Moreover, accumulation of multiubiquitin chains and direct oxidative injury to a proteasome were detected and inhibited by SOD1 after tFCI. These results suggest that SOD1 promotes the MDM2 pathway and the ubiquitin–proteasome system after tFCI and that production of reactive oxygen species after tFCI prevents p53 degradation by inhibiting both systems.

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46

FENG, LIN, Yan Dan Dan, Chen Ya Wen, Fletcher Emmanuella E, Shi Hai Feng, Han Bang Xing, and Zhou Yang. "Cloning, purification and enzymatic characterization of recombinant human Superoxide dismutase 1 expressed in Escherichia coli." Acta Biochimica Polonica 65, no. 2 (July 8, 2018): 235–40. http://dx.doi.org/10.18388/abp.2017_2350.

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Superoxide dismutase 1 (SOD1) is a metalloenzyme that catalyzes disproportion-action superoxide into molecular oxygen and hydrogen peroxide. In this study, the human SOD1 (hSOD1) gene was cloned, expressed, and purified. The hSOD1 gene was amplified from a pool of Bxpc3 cell cDNAs by PCR and cloned into expression vector pET-28a (+). The recombinant soluble hSOD1 was expressed in E.coli BL21 (DE3) at 37°C and purified by Nickel column affinity chromatography. The soluble hSOD1 was produced with a yield of 5.9 ug/mL medium. Considering that metal ions have a certain influence on the structure and activity of protein, we researched the influences of different concentrations of Cu2+ and Zn2+ on hSOD1 activity at induction and the time of activity detection. The results implied Cu2+ and Zn2+ can’t enhance SOD1 expression, however can improve the catalytic activity at induction. Furthermore, most of bivalent cations have an improve effect on enzyme activity at the time of detection.

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47

Noblanc, Anaīs, Alicia Klaassen, and Bernard Robaire. "The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice." Antioxidants 9, no. 2 (February 11, 2020): 151. http://dx.doi.org/10.3390/antiox9020151.

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There is growing evidence that the quality of spermatozoa decreases with age and that children of older fathers have a higher incidence of birth defects and genetic mutations. The free radical theory of aging proposes that changes with aging are due to the accumulation of damage induced by exposure to excess reactive oxygen species. We showed previously that absence of the superoxide dismutase 1 (Sod1) antioxidant gene results in impaired mechanisms of repairing DNA damage in the testis in young Sod1−/− mice. In this study, we examined the effects of aging and the Sod−/− mutation on mice epididymal histology and the expression of markers of oxidative damage. We found that both oxidative nucleic acid damage (via 8-hydroxyguanosine) and lipid peroxidation (via 4-hydroxynonenal) increased with age and in Sod1−/− mice. These findings indicate that lack of SOD1 results in an exacerbation of the oxidative damage accumulation-related aging phenotype.

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Nasibullin T.R., V. V. Erdman, Y. R. Timasheva, and I. A. Tuktarova. "Analysis of polymorphic DNA markers as potential predictors of myocardial infarction taking into account age." Biomics 12, no. 4 (2020): 455–59. http://dx.doi.org/10.31301/2221-6197.bmcs.2020-37.

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Myocardial infarction (MI) is a multifactorial polygenic disease. It develops because of the complex interaction between many environmental and genetic factors. In this investigation, we have studied associations of MI and rs1042034 (gene APOB), rs4420638 (gene APOC1) rs2070424 (gene SOD1) и rs662 (ген PON1) in an ethnically homogeneous group. The material for analysis was DNA samples of patients (365 men) with onset of MI at the age of 30 to 60 years and 292 essentially healthy men of the control group. The study revealed markers of increased risk of MI: SOD1*A/A, for men under 46 years of age (P=0.029, OR=1.96), APOC1*A/G (P=0.03, OR=2.01), for men over 48 years of age, and APOB*C/C (P=0.031OR=1.8).

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Ivansson, Emma L., Kate Megquier, Sergey V. Kozyrev, Eva Murén, Izabella Baranowska Körberg, Ross Swofford, Michele Koltookian, et al. "Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy." Proceedings of the National Academy of Sciences 113, no. 22 (May 16, 2016): E3091—E3100. http://dx.doi.org/10.1073/pnas.1600084113.

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Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10−5), and was associated with increased probability of developing DM (P = 4.8 × 10−6) and earlier onset of disease (P = 1.7 × 10−5). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds.

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Corradi, Nicolas, Beat Ruffner, Daniel Croll, Alexandre Colard, Ales Horák, and Ian R. Sanders. "High-Level Molecular Diversity of Copper-Zinc Superoxide Dismutase Genes among and within Species of Arbuscular Mycorrhizal Fungi." Applied and Environmental Microbiology 75, no. 7 (February 6, 2009): 1970–78. http://dx.doi.org/10.1128/aem.01974-08.

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ABSTRACT In the ecologically important arbuscular mycorrhizal fungi (AMF), Sod1 encodes a functional polypeptide that confers increased tolerance to oxidative stress and that is upregulated inside the roots during early steps of the symbiosis with host plants. It is still unclear whether its expression is directed at scavenging reactive oxygen species (ROS) produced by the host, if it plays a role in the fungus-host dialogue, or if it is a consequence of oxidative stress from the surrounding environment. All these possibilities are equally likely, and molecular variation at the Sod1 locus can possibly have adaptive implications for one or all of the three mentioned functions. In this paper, we analyzed the diversity of the Sod1 gene in six AMF species, as well as 14 Glomus intraradices isolates from a single natural population. By sequencing this locus, we identified a large amount of nucleotide and amino acid molecular diversity both among AMF species and individuals, suggesting a rapid divergence of its codons. The Sod1 gene was monomorphic within each isolate we analyzed, and quantitative PCR strongly suggest this locus is present as a single copy in G. intraradices. Maximum-likelihood analyses performed using a variety of models for codon evolution indicated that a number of amino acid sites most likely evolved under the regime of positive selection among AMF species. In addition, we found that some isolates of G. intraradices from a natural population harbor very divergent orthologous Sod1 sequences, and our analysis suggested that diversifying selection, rather than recombination, was responsible for the persistence of this molecular diversity within the AMF population.

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Journal articles on the topic 'SOD1 gene'

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