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Journal articles on the topic 'Kelch-like ECH-associated protein 1'

Author: Grafiati

Published: 5 June 2025

Last updated: 2 August 2025

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1

Scheffler, Matthias. "„Kelch-like ECH-associated protein 1“ (KEAP1)." Trillium Krebsmedizin 33, no. 4 (2024): 276–81. http://dx.doi.org/10.47184/tk.2024.04.8.

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In gesunden Zellen liegt das „Kelch-like ECH-associated protein 1“ (KEAP1) im Zellplasma vor und ist dort gebunden an das Protein NRF2. Der KEAP1-NRF2-Signalweg schützt die Zelle gegen oxidativen und metabolischen Stress. Zudem verhilft er den Zellen dazu, körperfremde chemische Verbindungen (Xenobiotika) zu tolerieren. Grundlegend hierfür sind über den KEAP1-NRF2-Signalweg angestoßene Mechanismen, die die Zelle vor dem Tod durch oxidativen Stress (Ferroptose) bewahren, sie entgiften und den Stoffwechsel reprogrammieren. Liegen jedoch Mutationen in einem Gen oder beiden Genen vor, wird der no

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2

Cai, Min, Li Tong, Beibei Dong, Wugang Hou, Likai Shi, and Hailong Dong. "Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2–related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning." Anesthesiology 126, no. 3 (2017): 507–21. http://dx.doi.org/10.1097/aln.0000000000001485.

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Abstract Background The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2–related factor 2 through multiple pathways. However, whether nuclear factor-E2–related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Methods Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five c

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3

Holland, Ryan, and James C. Fishbein. "Chemistry of the Cysteine Sensors in Kelch-Like ECH-Associated Protein 1." Antioxidants & Redox Signaling 13, no. 11 (2010): 1749–61. http://dx.doi.org/10.1089/ars.2010.3273.

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4

Sykiotis, Gerasimos P. "Keap1/Nrf2 Signaling Pathway." Antioxidants 10, no. 6 (2021): 828. http://dx.doi.org/10.3390/antiox10060828.

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Nuclear factor, erythroid 2-like transcription factor 2 (Nrf2) and its cytoplasmic inhibitor, kelch-like ECH-associated protein 1 (Keap1), comprise a redox-responsive endogenous antioxidant defense module that orchestrates the expression of cytoprotective genes to maintain homeostasis [...]

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5

Qu, Lingzhi, Ming Guo, Huajun Zhang, et al. "Characterization of the modification of Kelch-like ECH-associated protein 1 by different fumarates." Biochemical and Biophysical Research Communications 605 (May 2022): 9–15. http://dx.doi.org/10.1016/j.bbrc.2022.03.059.

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De Vita, Simona, Milena Masullo, Sabrina Grambone, Paloma Bermejo Bescós, Sonia Piacente, and Giuseppe Bifulco. "Demethylcalabaxanthone from Garcinia mangostana Exerts Antioxidant Effects through the Activation of the Nrf2 Pathway as Assessed via Molecular Docking and Biological Evaluation." Antioxidants 12, no. 11 (2023): 1980. http://dx.doi.org/10.3390/antiox12111980.

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Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation promotes the expression of antioxidant enzymes in response to rising oxidative stress, resulting in reactive oxygen species (ROS) detoxification and playing a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Moreover, the biological effects of Nrf2 pathway activation contribute to reducing apoptosis and enhancing cell survival. The activity of Nrf2 is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). Prompted by the recent results reporting the impact of xa

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Cairang, Nanjia, Yanran Wu, Shumeng Zhi, et al. "5-(3-(N-(Carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-carboxylic acid as a Keap1–Nrf2 inhibitor for cerebral ischemia/reperfusion injury treatment." RSC Advances 15, no. 2 (2025): 1052–59. https://doi.org/10.1039/d4ra06512c.

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The Keap1 (Kelch-like ECH-Associating Protein 1)–Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2)-ARE (Antioxidant Response Element) signaling pathway plays a crucial role in the oxidative stress response and has been linked to the development and progression of various diseases.

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Mulvaney, Kathleen M., Jacob P. Matson, Priscila F. Siesser, et al. "Identification and Characterization of MCM3 as a Kelch-like ECH-associated Protein 1 (KEAP1) Substrate." Journal of Biological Chemistry 291, no. 45 (2016): 23719–33. http://dx.doi.org/10.1074/jbc.m116.729418.

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9

Sogabe, Satoshi, Kotaro Sakamoto, Yusuke Kamada, Akito Kadotani, Yasunori Fukuda, and Jun-ichi Sakamoto. "Discovery of a Kelch-like ECH-associated protein 1-inhibitory tetrapeptide and its structural characterization." Biochemical and Biophysical Research Communications 486, no. 3 (2017): 620–25. http://dx.doi.org/10.1016/j.bbrc.2017.03.038.

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10

Long, Xiangju, Zhe Liu, Yanan Sun, and Hong Zhang. "The Protective Role of Nrf2 in Renal Tubular Cells in Oxidised Low-Density Lipoprotein-Induced Fibrosis." Analytical Cellular Pathology 2023 (March 11, 2023): 1–8. http://dx.doi.org/10.1155/2023/4134928.

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Background: CD36 is the receptor of oxidised low-density lipoprotein (OxLDL) in renal tubular epithelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the key factor in the activation of the Nrf2 signalling pathway and the regulation of oxidative stress. Kelch-like ECH-associated protein 1 (Keap1) is known as an Nrf2 inhibitor. Methods: We used OxLDL and Nrf2 inhibitors at different concentrations and durations to treat renal tubular epithelial cells; the expression of CD36 and cytoplasmic and nucleic Nrf2 and E-cadherin in those cells were observed by Western blot and reverse-t

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11

Unoki, Takamitsu, Masahiro Akiyama, and Yoshito Kumagai. "Nrf2 Activation and Its Coordination with the Protective Defense Systems in Response to Electrophilic Stress." International Journal of Molecular Sciences 21, no. 2 (2020): 545. http://dx.doi.org/10.3390/ijms21020545.

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Molecular responses mediated by sensor proteins are important for biological defense against electrophilic stresses, such as xenobiotic electrophile exposure. NF-E2-related factor 2 (Nrf2) has an essential function as a master regulator of such cytoprotective molecular responses along with sensor protein Kelch-like ECH-associated protein 1. This review focuses on Nrf2 activation and its involvement with the protective defense systems under electrophilic stresses integrated with our recent findings that reactive sulfur species (RSS) mediate detoxification of electrophiles. The Nrf2 pathway does

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12

Taliani, Sabrina, Federico Da Settimo, Claudia Martini, Sonia Laneri, Ettore Novellino, and Giovanni Greco. "Exploiting the Indole Scaffold to Design Compounds Binding to Different Pharmacological Targets." Molecules 25, no. 10 (2020): 2331. http://dx.doi.org/10.3390/molecules25102331.

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Several indole derivatives have been disclosed by our research groups that have been collaborating for nearly 25 years. The results of our investigations led to a variety of molecules binding selectively to different pharmacological targets, specifically the type A γ-aminobutyric acid (GABAA) chloride channel, the translocator protein (TSPO), the murine double minute 2 (MDM2) protein, the A2B adenosine receptor (A2B AR) and the Kelch-like ECH-associated protein 1 (Keap1). Herein, we describe how these works were conceived and carried out thanks to the versatility of indole nucleus to be exploi

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13

Kumagai, Yoshito, Hironori Kanda, Yasuhiro Shinkai, and Takashi Toyama. "The Role of the Keap1/Nrf2 Pathway in the Cellular Response to Methylmercury." Oxidative Medicine and Cellular Longevity 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/848279.

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Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins with reactive thiols, resulting in the formation of protein adducts. While such protein modifications, referred to asS-mercuration, are thought to be associated with the enzyme dysfunction and cellular damage caused by MeHg exposure, the current consensus is that (1) there is a cellular response to MeHg through the activation of NF-E2-related factor 2 (Nrf2) coupled toS-mercuration of its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), and (2) the Keap1/Nrf2 pathway protects agains

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14

Canning, Peter, and Alex N. Bullock. "New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases." Biochemical Society Transactions 42, no. 1 (2014): 103–7. http://dx.doi.org/10.1042/bst20130215.

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E3 ubiquitin ligases that direct substrate proteins to the ubiquitin–proteasome system are promising, though largely unexplored drug targets both because of their function and their remarkable specificity. CRLs [Cullin–RING (really interesting new gene) ligases] are the largest group of E3 ligases and function as modular multisubunit complexes constructed around a Cullin-family scaffold protein. The Cul3-based CRLs uniquely assemble with BTB (broad complex/tramtrack/bric-à-brac) proteins that also homodimerize and perform the role of both the Cullin adapter and the substrate-recognition compon

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15

Zhang, Yuesheng, and Gary B. Gordon. "A strategy for cancer prevention: Stimulation of the Nrf2-ARE signaling pathway." Molecular Cancer Therapeutics 3, no. 7 (2004): 885–93. http://dx.doi.org/10.1158/1535-7163.885.3.7.

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Abstract Many genes, with products involved in the protection of cells against carcinogens, oxidants, and other toxic chemicals, are under the transcriptional control of a simple DNA regulatory element [i.e., the antioxidant response element (ARE)]. One or more functional AREs have been confirmed or are believed to exist in the upstream region of many anticarcinogenic/antioxidant genes and have been shown to mediate the coordinate transcriptional up-regulation of these genes by many chemical agents [i.e., the ARE-mediated inducers]. There is strong evidence that increased expression of ARE-reg

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16

Pallesen, Jakob S., Dilip Narayanan, Kim T. Tran, et al. "Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds." Journal of Medicinal Chemistry 64, no. 8 (2021): 4623–61. http://dx.doi.org/10.1021/acs.jmedchem.0c02094.

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17

Strachan, Gordon D., Kathleen L. Morgan, Linda L. Otis, et al. "Fetal Alz-50 Clone 1 Interacts with the Human Orthologue of the Kelch-like Ech-Associated Protein†." Biochemistry 43, no. 38 (2004): 12113–22. http://dx.doi.org/10.1021/bi0494166.

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18

Edwards, Megan R., Britney Johnson, Chad E. Mire, et al. "The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway." Cell Reports 6, no. 6 (2014): 1017–25. https://doi.org/10.5281/zenodo.13465828.

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(Uploaded by Plazi for the Bat Literature Project) Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of

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19

Edwards, Megan R., Britney Johnson, Chad E. Mire, et al. "The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway." Cell Reports 6, no. 6 (2014): 1017–25. https://doi.org/10.5281/zenodo.13465828.

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(Uploaded by Plazi for the Bat Literature Project) Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of

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20

Edwards, Megan R., Britney Johnson, Chad E. Mire, et al. "The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway." Cell Reports 6, no. 6 (2014): 1017–25. https://doi.org/10.5281/zenodo.13465828.

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(Uploaded by Plazi for the Bat Literature Project) Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of

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21

Edwards, Megan R., Britney Johnson, Chad E. Mire, et al. "The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway." Cell Reports 6, no. 6 (2014): 1017–25. https://doi.org/10.5281/zenodo.13465828.

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(Uploaded by Plazi for the Bat Literature Project) Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of

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22

Edwards, Megan R., Britney Johnson, Chad E. Mire, et al. "The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway." Cell Reports 6, no. 6 (2014): 1017–25. https://doi.org/10.5281/zenodo.13465828.

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(Uploaded by Plazi for the Bat Literature Project) Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of

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23

Wilson, Carter J., Megan Chang, Mikko Karttunen, and Wing-Yiu Choy. "KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability." International Journal of Molecular Sciences 22, no. 10 (2021): 5408. http://dx.doi.org/10.3390/ijms22105408.

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We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experi

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Ngo, Vy, Nadun C. Karunatilleke, Anne Brickenden, Wing-Yiu Choy, and Martin L. Duennwald. "Oxidative Stress-Induced Misfolding and Inclusion Formation of Nrf2 and Keap1." Antioxidants 11, no. 2 (2022): 243. http://dx.doi.org/10.3390/antiox11020243.

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Cells that experience high levels of oxidative stress respond by inducing antioxidant proteins through activation of the protein transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is negatively regulated by the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (Keap1), which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we studied protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptibl

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Edwards, Megan R., та Christopher F. Basler. "Marburg Virus VP24 Protein Relieves Suppression of the NF–κB Pathway Through Interaction With Kelch-like ECH-Associated Protein 1". Journal of Infectious Diseases 212, suppl 2 (2015): S154—S159. http://dx.doi.org/10.1093/infdis/jiv050.

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Lazzara, Phillip R., Brian P. David, Aparna Ankireddy, et al. "Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability." Journal of Medicinal Chemistry 63, no. 12 (2019): 6547–60. http://dx.doi.org/10.1021/acs.jmedchem.9b01074.

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27

Abdelmawgood, Islam Ahmed, Noha Ahmed Mahana, Abeer Mahmoud Badr, et al. "Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway." Marine Drugs 21, no. 8 (2023): 455. http://dx.doi.org/10.3390/md21080455.

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Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antio

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Wu, Shouquan, Xiaojuan Ding, Qianlan Yang, Minggui Wang, and Jian-Qing He. "Association of Three SNPs Loci of Kelch-Like-ECH-Associated Protein 1 (Human) with Tuberculosis in Chinese Han Population." International Journal of General Medicine Volume 15 (August 2022): 6365–72. http://dx.doi.org/10.2147/ijgm.s373555.

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Housand, Conrad, Nil Roy, Tine Wyseure, et al. "Abstract C126: Translational pharmacokinetic/pharmacodynamic (PK/PD) modeling of novel covalent Kelch-like ECH-associated protein 1 (KEAP1) activators." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): C126. http://dx.doi.org/10.1158/1535-7163.targ-23-c126.

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Abstract Introduction: The KEAP1-nuclear factor erythroid 2-related factor 2 (NRF2) signaling axis is a key homeostatic mechanism for cells to maintain redox balance. In oxidative stress, reactive oxygen species (ROS) modify residues on KEAP1, impairing its binding and ubiquitination of NRF2. This leads to an accumulation and translocation of NRF2 to the nucleus where it increases transcription of genes for antioxidant response [Pillai 2022]. The KEAP1-NRF2 pathway is hijacked in cancers through NRF2 gain of function or KEAP1 loss of function mutations leading to aberrant activation of NRF2. W

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Zhong, Mengqi, Andrew Lynch, Samantha N. Muellers, et al. "Interaction Energetics and Druggability of the Protein–Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2)." Biochemistry 59, no. 4 (2019): 563–81. http://dx.doi.org/10.1021/acs.biochem.9b00943.

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Shilovsky, Gregory A., and Daria V. Dibrova. "Regulation of Cell Proliferation and Nrf2-Mediated Antioxidant Defense: Conservation of Keap1 Cysteines and Nrf2 Binding Site in the Context of the Evolution of KLHL Family." Life 13, no. 4 (2023): 1045. http://dx.doi.org/10.3390/life13041045.

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Keap1 (Kelch-like ECH-associated protein 1) is one of the major negative regulators of the transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2), which induces the expression of numerous proteins defending the cell against different stress conditions. Keap1 is generally negatively regulated by post-translational modification (mostly via its cysteine residues) and interaction with other proteins that compete with Nrf2 for binding. Cysteine residues in Keap1 have different effects on protein regulation, as basic residues (Lys, Arg, and His) in close proximity to them increase c

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Liu, Xiu-Fen, Dan-Dan Zhou, Tian Xie, et al. "Nrf2, a Potential Therapeutic Target against Oxidative Stress in Corneal Diseases." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/2326178.

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Corneal diseases are one of the major causes of blindness worldwide. Conservative medical agents, which may prevent sight-threatening corneal disease progression, are urgently desired. Numerous evidences have revealed the involvement of oxidative stress in various corneal diseases, such as corneal wound healing and Fuchs endothelial corneal dystrophy (FECD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology- (ECH-) associated protein 1 (Keap1)/antioxidant response element (ARE) signaling is well known as one of the main antioxidative

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Chen, Ming, Jing Luo, Hongwu Ji, et al. "The Preventive Mechanism of Anserine on Tert-Butyl Hydroperoxide-Induced Liver Injury in L-02 Cells via Regulating the Keap1-Nrf2 and JNK-Caspase-3 Signaling Pathways." Marine Drugs 21, no. 9 (2023): 477. http://dx.doi.org/10.3390/md21090477.

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Anserine is a naturally occurring histidine dipeptide with significant antioxidant activities. This study aimed to investigate the preventive mechanism of anserine on tert-butyl hydroperoxide (TBHP)-induced liver damage in a normal human liver cell line (L-02 cells). The L-02 cells were pretreated with anserine (10, 20, and 40 mmol/L) and then induced with 400 μmol/L of TBHP for 4 h. The results showed that the survival rates of L-02 cells and the contents of GSH were significantly increased with the pretreatment of anserine; the activities of alanine aminotransferase (ALT) and aspartate amino

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Liu, Chang, Yaohui Zhu, Zhenxiang Lu та ін. "Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway". International Journal of Environmental Research and Public Health 17, № 1 (2019): 138. http://dx.doi.org/10.3390/ijerph17010138.

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Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute he

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Leinonen, Hanna M., Emilia Kansanen, Petri Pölönen, Merja Heinäniemi, and Anna-Liisa Levonen. "Dysregulation of the Keap1–Nrf2 pathway in cancer." Biochemical Society Transactions 43, no. 4 (2015): 645–49. http://dx.doi.org/10.1042/bst20150048.

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Accumulating evidence suggests that dysregulation of the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor E2-related factor 2 (Nrf2) pathway resulting in constitutively active Nrf2 and increased expression of cytoprotective Nrf2 target genes, has a pivotal role in cancer. Cancer cells are able to hijack the Keap1–Nrf2 system via multiple mechanisms leading to enhanced chemo- and radio-resistance and proliferation via metabolic reprogramming as well as inhibition of apoptosis. In this mini-review, we will describe the mechanisms leading to increased Nrf2 activity in cancer with a focu

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Cheng, Yao, Tsz Tin Yu, Ellen M. Olzomer, et al. "Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents." Molecules 30, no. 9 (2025): 1938. https://doi.org/10.3390/molecules30091938.

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The Warburg effect, a unique glycolytic phenomenon in cancer cells, presents a promising target for developing selective anticancer agents. Previously, BH10, a hit compound disrupting glycolytic metabolism, was identified via phenotypic screening, with Kelch-like ECH-associated protein 1 (Keap1) proposed as a potential target. To enhance its potency and selectivity, a library of BH10-derived salt compounds was synthesized. Among these, 7b exhibited nanomolar anticancer activity (IC50 = 22.97 nM) and a high selectivity ratio (IC50 of non-cancerous cells/IC50 of cancer cells = 41.43). Molecular

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Tian, Wang, Montserrat Rojo de la Vega, Cody J. Schmidlin, Aikseng Ooi, and Donna D. Zhang. "Kelch-like ECH-associated protein 1 (KEAP1) differentially regulates nuclear factor erythroid-2–related factors 1 and 2 (NRF1 and NRF2)." Journal of Biological Chemistry 293, no. 6 (2017): 2029–40. http://dx.doi.org/10.1074/jbc.ra117.000428.

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Xu, Iris Ming-Jing, Robin Kit-Ho Lai, Shu-Hai Lin, et al. "Transketolase counteracts oxidative stress to drive cancer development." Proceedings of the National Academy of Sciences 113, no. 6 (2016): E725—E734. http://dx.doi.org/10.1073/pnas.1508779113.

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Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer ce

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Richardson, Benjamin G., Atul D. Jain, Haranatha R. Potteti, et al. "Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors." Journal of Medicinal Chemistry 61, no. 17 (2018): 8029–47. http://dx.doi.org/10.1021/acs.jmedchem.8b01133.

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Alves, Renata, Camila Liyoko Suehiro, Flavia Garcia de Oliveira, et al. "Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption." Journal of Applied Physiology 128, no. 1 (2020): 59–69. http://dx.doi.org/10.1152/japplphysiol.00201.2019.

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The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups ( n = 10). After 12 wk, the energy intake and body weight in the groups were similar. Maximum exercise testing, resting energy expenditure, resting oxygen consumption, and carbon dioxide productio

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Nettleton, Margaret, Luis E. Almeida, Sayuri Kamimura, Richard G. Lee, Gene Hung, and Zena Quezado. "Antisense Oligonucleotide Against Kelch-like Ech-Associated protein1 Ameliorates Liver Injury in Sickle Cell Mice." Blood 128, no. 22 (2016): 1294. http://dx.doi.org/10.1182/blood.v128.22.1294.1294.

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Abstract A great deal of evidence links the manifestations and associated morbidities of sickle cell disease (SCD) to ischemia/reperfusion injury and increased oxidative stress. Recent studies using humanized SCD mice show that thermal and mechanical hyperalgesia is associated with microglia activation and increased oxidative stress in the spinal cord, which are all ameliorated by treatment with antioxidants. In kidneys of SCD mice, at baseline, there is elevated heme content and increased oxidative stress (increased lipid peroxidation and severe medullary congestion). Synthesis inhibition of

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Zhou, Shipeng, Qiuhua Tan, Bingjian Wen, et al. "Galacto-Oligosaccharide Alleviates Alcohol-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation." Metabolites 12, no. 9 (2022): 867. http://dx.doi.org/10.3390/metabo12090867.

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Background: Alcoholic liver disease (ALD) is a primary cause of mortality and morbidity worldwide. Oxidative stress and inflammation are important pathogenic factors contributing to ALD. Methods: We investigated the protective mechanism of galacto-oligosaccharide (GOS) against ALD through their antioxidant and anti-inflammatory activities by performing in vivo and in vitro experiments. Results: Western blot and RT‒PCR results indicated that the expression of cytochrome P450 protein 2E1 (CYP2E1) in liver tissues and L02 cells was reduced in the GOS-treated mice compared with the model group. In

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Luo, Ying, Wei Zhang, Liang Xu, Yajun Chen, Yao Xu, and Lin Yuan. "Long Non-Coding RNA PVT1 Regulates the Resistance of the Breast Cancer Cell Line MDA-MB-231 to Doxorubicin via Nrf2." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382098076. http://dx.doi.org/10.1177/1533033820980763.

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Triple-negative breast cancer (TNBC) is one of the most common malignant tumor types in females and its drug resistance is a major clinical issue. An increasing number of long non-coding RNAs (lncRNAs) have been reported as key regulators of drug resistance in TNBC. Plasmacytoma variant translocation 1 (PVT1) has been proved to promote the development of various cancer types. The present study suggested that PVT1 enhances the resistance of the TNBC cell line MDA-MB-231 to doxorubicin and uncovered the molecular mechanism. PVT1 function assays and its target gene analyses were performed. We rev

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Karunatilleke, Nadun C., Courtney S. Fast, Vy Ngo, et al. "Nrf2, the Major Regulator of the Cellular Oxidative Stress Response, is Partially Disordered." International Journal of Molecular Sciences 22, no. 14 (2021): 7434. http://dx.doi.org/10.3390/ijms22147434.

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription regulator that plays a pivotal role in coordinating the cellular response to oxidative stress. Through interactions with other proteins, such as Kelch-like ECH-associated protein 1 (Keap1), CREB-binding protein (CBP), and retinoid X receptor alpha (RXRα), Nrf2 mediates the transcription of cytoprotective genes critical for removing toxicants and preventing DNA damage, thereby playing a significant role in chemoprevention. Dysregulation of Nrf2 is linked to tumorigenesis and chemoresistance, making Nrf2 a promising target for

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Guon, Tae Eun, and Ha Sook Chung. "[10]-Gingerol from Zingiber Officinale Reduces Oxidative Stress via the ERK/Nrf2/HO-1 Signaling Pathway in Human Keratinocytes." Korean Tea Society 28, no. 2 (2022): 59–67. http://dx.doi.org/10.29225/jkts.2022.28.2.59.

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The present study was designed to investigate the molecular mechanisms of bioactive components against mild oxidative stress in human keratinocytes (HaCaTs). Solvent extraction and fractionation of the rhizomes of Zingiber officinale resulted in the isolation of [10]-gingerol. At concentrations of 1, 3, and 5 µM [10]-gingerol dose-dependently increased HO-1 (heme oxygenase-1) mRNA and protein levels, with a significant effect at 5 µM. This augmentation of HO-1 by [10]-gingerol was attributed to the upregulation of Nrf2 (nuclear factor erythroid 2-related factor 2), which markedly reduced the c

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Singh, Seema, Abdulsalam, and Tahseen Raza. "A critique on cell signallings involve in colorectal cancer." Indian Journal of Clinical Anatomy and Physiology 9, no. 3 (2022): 161–65. http://dx.doi.org/10.18231/j.ijcap.2022.035.

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Colorectal carcinogenesis (CRC) is a significant health issue in developing countries. It ranks as the third most common outcome of cancer death. New drugs are required to lower the prevalence of this ailment despite a multitude of therapeutic choices. As CRC develops, several signaling pathways pathways are activated. Among the important signaling pathways are the p53, Delta-Notch, Wnt/-catenin, Salvador-Warts-Hippo (SWH), and Kelch-like ECH assocd protein 1 pathways. This paper summarises the aetiology of CRC as well as the related death of cells and cell signal transduction pathways.

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Wang, Xin-Qin, Rong-Ping Liu, Jing Wang, et al. "Wedelolactone facilitates the early development of parthenogenetically activated porcine embryos by reducing oxidative stress and inhibiting autophagy." PeerJ 10 (July 25, 2022): e13766. http://dx.doi.org/10.7717/peerj.13766.

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Wedelolactone (WDL) is a coumaryl ether compound extracted from the traditional Chinese medicinal plant, Eclipta prostrata L. It is a natural polyphenol that exhibits a variety of pharmacological activities, such as anti-inflammatory, anti-free radical, and antioxidant activities in the bone, brain, and ovary. However, its effect on embryonic development remains unknown. The present study explored the influence of WDL supplementation of porcine oocytes culture in vitro on embryonic development and the underlying mechanisms and its effect on the levels of Kelch-like ECH-associated protein 1/nuc

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Lin, Chiao-Yun, Chen-Bin Chang, Ren-Chin Wu, et al. "Glucose Activates Lysine-Specific Demethylase 1 through the KEAP1/p62 Pathway." Antioxidants 10, no. 12 (2021): 1898. http://dx.doi.org/10.3390/antiox10121898.

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Endometrial cancer incidence increases annually. Several risk factors, including high glucose intake, are associated with endometrial cancer. We investigated whether glucose affects lysine-specific demethylase 1 (LSD1) expression and the responsible molecular mechanisms. A high concentration of glucose stimulated p62 phosphorylation and increased LSD1 protein expression. Knockdown of p62 or treatment with mammalian target of rapamycin (mTOR), transforming growth factor-β activated kinase 1 (TAK1), casein kinase 1 (CK1), and protein kinase C (PKC) inhibitors abrogated glucose-regulated LSD1 exp

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Liu, Hongcheng, Tong Sun, He Gao, et al. "Bioinformatics-Assisted Discovery of Antioxidant Cyclic Peptides from Corn Gluten Meal." Foods 14, no. 10 (2025): 1709. https://doi.org/10.3390/foods14101709.

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Using a multidisciplinary approach, this paper was designed to prepare, identify, and characterize novel maize antioxidant cyclic peptides from protein hydrolysate of corn gluten meal (CGM). A bioinformatics approach was used to identify the best protease, and the results showed that papain+subtilisin was most likely to produce antioxidant cyclic peptides. The result of the enzymatic hydrolysis validation experiment showed that hydrolysate by papain+subtilisin yielded the highest concentration of cyclic peptide (67.14 ± 1.88%) and remarkable DPPH, ABTS, and hydroxyl radical scavenging rates (8

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Zhang, Ping, Anju Singh, Srinivasan Yegnasubramanian, et al. "Loss of Kelch-Like ECH-Associated Protein 1 Function in Prostate Cancer Cells Causes Chemoresistance and Radioresistance and Promotes Tumor Growth." Molecular Cancer Therapeutics 9, no. 2 (2010): 336–46. http://dx.doi.org/10.1158/1535-7163.mct-09-0589.

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