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1

ElFessi, Rym, Oussema Khamessi, Michel De Waard, et al. "Structure–Function Relationship of a Novel MTX-like Peptide (MTX1) Isolated and Characterized from the Venom of the Scorpion Maurus palmatus." International Journal of Molecular Sciences 25, no. 19 (2024): 10472. http://dx.doi.org/10.3390/ijms251910472.

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Maurotoxin (MTX) is a 34-residue peptide from Scorpio maurus venom. It is reticulated by four disulfide bridges with a unique arrangement compared to other scorpion toxins that target potassium (K+) channels. Structure–activity relationship studies have not been well performed for this toxin family. The screening of Scorpio maurus venom was performed by different steps of fractionation, followed by the ELISA test, using MTX antibodies, to isolate an MTX-like peptide. In vitro, in vivo and computational studies were performed to study the structure–activity relationship of the new isolated peptide. We isolated a new peptide designated MTX1, structurally related to MTX. It demonstrated toxicity on mice eight times more effectively than MTX. MTX1 blocks the Kv1.2 and Kv1.3 channels, expressed in Xenopus oocytes, with IC50 values of 0.26 and 180 nM, respectively. Moreover, MTX1 competitively interacts with both 125I-apamin (IC50 = 1.7 nM) and 125I-charybdotoxin (IC50 = 5 nM) for binding to rat brain synaptosomes. Despite its high sequence similarity (85%) to MTX, MTX1 exhibits a higher binding affinity towards the Kv1.2 and SKCa channels. Computational analysis highlights the significance of specific residues in the β-sheet region, particularly the R27, in enhancing the binding affinity of MTX1 towards the Kv1.2 and SKCa channels.
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2

Abdel-Rahman, Mohamed A., Mohamed Alaa A. Omran, Ismail M. Abdel-Nabi, Hitoshi Ueda, and Alistair McVean. "Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes." Toxicon 53, no. 3 (2009): 349–59. http://dx.doi.org/10.1016/j.toxicon.2008.12.007.

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3

Abdelrahman, Mohamed, Mohamed Omran, Ismail Abdel-Nabi, Metwally Abdalla, and Azza Elelemi. "Hormonal alterations elicited by the scorpion venom of Scorpio maurus palmatus, in vivo study." Egyptian Society of Clinical Toxicology Journal 11, no. 1 (2023): 1–11. http://dx.doi.org/10.21608/esctj.2022.176913.1019.

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4

Elrayess, Ranwa A., Mahmoud E. Mohallal, Yomn M. El-Shahat, et al. "Cytotoxic Effects of Smp24 and Smp43 Scorpion Venom Antimicrobial Peptides on Tumour and Non-tumour Cell Lines." International Journal of Peptide Research and Therapeutics 26, no. 3 (2019): 1409–15. http://dx.doi.org/10.1007/s10989-019-09932-1.

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Abstract Smp24 and Smp43 are novel cationic AMPs identified from the venom of the Egyptian scorpion Scorpio maurus palmatus, having potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards three non-tumour cell lines (CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HACAT (human skin keratinocytes) and two acute leukaemia cell lines (myeloid (KG1a) and lymphoid (CCRF-CEM) leukaemia cell lines) using a combination of biochemical and imaging techniques. Smp24 and Smp43 (4–256 µg/mL) decreased the cell viability (as measured by intracellular ATP) of all cells tested, although keratinocytes were markedly less sensitive. Cell membrane leakage as evidenced by the release of lactate dehydrogenase was evident throughout and was confirmed by scanning electron microscope studies.
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5

Abdel-Rahman, Mohamed A., Veronica Quintero-Hernandez, and Lourival D. Possani. "Venom proteomic and venomous glands transcriptomic analysis of the Egyptian scorpion Scorpio maurus palmatus (Arachnida: Scorpionidae)." Toxicon 74 (November 2013): 193–207. http://dx.doi.org/10.1016/j.toxicon.2013.08.064.

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6

Abdel-Rahman, Mohamed A., Ahmad K. Mohammed, Sherifa H. Ahmed, Yaser S. Binnaser, and Ismail M. Abdel-Nabi. "Antidiabetic effect of the scorpion Scorpio maurus palmatus body extract using alloxan-induced diabetic mice model." Journal of Taibah University for Science 13, no. 1 (2019): 504–13. http://dx.doi.org/10.1080/16583655.2019.1599184.

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7

Deng, Ze, Yahua Gao, Tienthanh Nguyen, et al. "The Potent Antitumor Activity of Smp43 against Non-Small-Cell Lung Cancer A549 Cells via Inducing Membranolysis and Mitochondrial Dysfunction." Toxins 15, no. 5 (2023): 347. http://dx.doi.org/10.3390/toxins15050347.

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Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its impact on non-small-cell lung cancer (NSCLC) cell lines has not been previously investigated. This study aimed to determine the cytotoxicity of Smp43 towards various NSCLC cell lines, particularly A549 cells with an IC50 value of 2.58 μM. The results indicated that Smp43 was internalized into A549 cells through membranolysis and endocytosis, which caused cytoskeleton disorganization, a loss of mitochondrial membrane potential, an accumulation of reactive oxygen species (ROS), and abnormal apoptosis, cell cycle distribution, and autophagy due to mitochondrial dysfunction. Additionally, the study explored the in vivo protective effect of Smp43 in xenograft mice. The findings suggest that Smp43 has potential anticarcinoma properties exerted via the inducement of cellular processes related to cell membrane disruption and mitochondrial dysfunction.
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8

Abdel-Rahman, Mohamed, Mohamed Omran, Ismail Abdel-Nabi, Azza El-Elemi, and Metwally Abdalla. "In vitro cytotoxicity induced by the scorpion venom of Scorpio maurus palmatus inhabiting different localities in Egypt." Egyptian Society of Clinical Toxicology Journal 10, no. 2 (2022): 59–74. http://dx.doi.org/10.21608/esctj.2022.164039.1015.

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9

Harrison, Patrick L., Mohamed A. Abdel-Rahman, Peter N. Strong, Mohamed M. Tawfik, and Keith Miller. "Characterisation of three alpha-helical antimicrobial peptides from the venom of Scorpio maurus palmatus." Toxicon 117 (July 2016): 30–36. http://dx.doi.org/10.1016/j.toxicon.2016.03.014.

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10

So, Wai Lok, Thomas C. N. Leung, Wenyan Nong, William G. Bendena, Sai Ming Ngai, and Jerome H. L. Hui. "Transcriptomic and proteomic analyses of venom glands from scorpions Liocheles australasiae, Mesobuthus martensii, and Scorpio maurus palmatus." Peptides 146 (December 2021): 170643. http://dx.doi.org/10.1016/j.peptides.2021.170643.

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11

Guo, Ruiyin, Xuewen Chen, Tienthanh Nguyen, et al. "The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation." Toxins 14, no. 9 (2022): 590. http://dx.doi.org/10.3390/toxins14090590.

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Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been reported earlier. However, its effects on mitochondrial functions and ROS accumulation in human lung cancer cells remain unknown. In the current study, we discovered that Smp24 can interact with the cell membrane and be internalized into A549 cells via endocytosis, followed by targeting mitochondria and affect mitochondrial function, which significantly causes ROS overproduction, altering mitochondrial membrane potential and the expression of cell cycle distribution-related proteins, mitochondrial apoptotic pathway, MAPK, as well as PI3K/Akt/mTOR/FAK signaling pathways. In summary, the antitumor effect of Smp24 against A549 cells is related to the induction of apoptosis, autophagy plus cell cycle arrest via mitochondrial dysfunction, and ROS accumulation. Accordingly, our findings shed light on the anticancer mechanism of Smp24, which may contribute to its further development as a potential agent in the treatment of lung cancer cells.
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12

Abdel-Rahman, Mohamed A., Mohamed Alaa A. Omran, Ismail M. Abdel-Nabi, Omimah A. Nassier, and Brandon J. Schemerhorn. "Neurotoxic and cytotoxic effects of venom from different populations of the Egyptian Scorpio maurus palmatus." Toxicon 55, no. 2-3 (2010): 298–306. http://dx.doi.org/10.1016/j.toxicon.2009.08.003.

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13

Nguyen, Tienthanh, Ruiyin Guo, Jinwei Chai, et al. "Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro." Toxins 14, no. 10 (2022): 717. http://dx.doi.org/10.3390/toxins14100717.

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Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.
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14

Amen, Radwa Abdallnasser. "Therapeutic potential and characteristics of Smp43 peptide (scorpion venom) and its interaction with cellular signaling pathways: A review." Innovative Medicines & Omics 1, no. 1 (2024): 4353. http://dx.doi.org/10.36922/imo.4353.

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Smp43 peptide, derived from the venom of the scorpion Scorpio Maurus Palmatus, exhibits significant potential across a range of therapeutic domains due to its diverse biological actions. Interestingly, Smp43 possesses robust anti-inflammatory and antioxidant properties, enabling it to scavenge free radicals and suppress pro-inflammatory cytokines. This dual functionality makes Smp43 a viable candidate for the treatment of conditions associated with oxidative stress and chronic inflammation. Furthermore, its broad-spectrum antibacterial activity is indicative of its efficacy against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains. This antibacterial action is primarily characterized by the disruption of bacterial membranes and interference with intracellular processes. In addition, Smp43’s antiviral potential is highlighted by its broad-spectrum activity against viral infections and its ability to modulate host immune responses. The peptide also shows promise in cancer therapy, as it has been demonstrated to induce apoptosis and autophagy, impacting apoptotic pathways, the production of reactive oxygen species, and cellular autophagy mechanisms. In conclusion, Smp43 has the capacity to modulate key signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and ERK/MAPK, thereby influencing crucial cellular processes such as autophagy, metabolism, cell growth, and survival.
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15

Guo, Ruiyin, Junfang Liu, Jinwei Chai, Yahua Gao, Mohamed A. Abdel-Rahman, and Xueqing Xu. "Scorpion Peptide Smp24 Exhibits a Potent Antitumor Effect on Human Lung Cancer Cells by Damaging the Membrane and Cytoskeleton In Vivo and In Vitro." Toxins 14, no. 7 (2022): 438. http://dx.doi.org/10.3390/toxins14070438.

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Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells.
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16

Bertelsen, Magnus, Melissa M. Lacey, Tim Nichol, and Keith Miller. "Mechanistic Insight into the Early Stages of Toroidal Pore Formation by the Antimicrobial Peptide Smp24." Pharmaceutics 15, no. 10 (2023): 2399. http://dx.doi.org/10.3390/pharmaceutics15102399.

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The antimicrobial peptide Smp24, originally derived from the venom of Scorpio maurus palmatus, is a promising candidate for further drug development. However, before doing so, greater insight into the mechanism of action is needed to construct a reliable structure–activity relationship. The aim of this study was to specifically investigate the critical early stages of peptide-induced membrane disruption. Single-channel current traces were obtained via planar patch-clamp electrophysiology, with multiple types of pore-forming events observed, unlike those expected from the traditional, more rigid mechanistic models. To better understand the molecular-level structures of the peptide-pore assemblies underlying these observed conductance events, molecular dynamics simulations were used to investigate the peptide structure and orientation both before and during pore formation. The transition of the peptides to transmembrane-like states within disordered toroidal pores occurred due to a peptide-induced bilayer-leaflet asymmetry, explaining why pore stabilization does not always follow pore nucleation in the experimental observations. To fully grasp the structure–activity relationship of antimicrobial peptides, a more nuanced view of the complex and dynamic mechanistic behaviour must be adopted.
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17

Rutin, J. "The burrowing activity of scorpions (Scorpio maurus palmatus) and their potential contribution to the erosion of Hamra soils in Karkur, central Israel." Geomorphology 15, no. 2 (1996): 159–68. http://dx.doi.org/10.1016/0169-555x(95)00120-t.

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18

Rawson, Kirstie M., Melissa M. Lacey, Peter N. Strong, and Keith Miller. "Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria." International Journal of Molecular Sciences 23, no. 14 (2022): 7979. http://dx.doi.org/10.3390/ijms23147979.

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Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure–function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.
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19

El-Bitar, Alaa M. H., Moustafa Sarhan, Mohamed A. Abdel-Rahman, et al. "Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus." International Journal of Peptide Research and Therapeutics 26, no. 2 (2019): 811–21. http://dx.doi.org/10.1007/s10989-019-09888-2.

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20

Xojimurodov, Davronjon Ikramaliyevich, and Region Teacher of the Faculty of Medicine Tashkent. "VIROCIDAL ACTIVITY OF EGYPTIAN SCORPION VENOMS AGAINST HEPATITIS C VIRUS." Multidisciplinary Journal of Science and Technology 4, no. 2 (2024): 169–73. https://doi.org/10.5281/zenodo.10666955.

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Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions.
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21

Altafaj, Xavier, Julien France, Janos Almassy, et al. "Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification." Biochemical Journal 406, no. 2 (2007): 309–15. http://dx.doi.org/10.1042/bj20070453.

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We have previously shown that MCa (maurocalcine), a toxin from the venom of the scorpion Maurus palmatus, binds to RyR1 (type 1 ryanodine receptor) and induces strong modifications of its gating behaviour. In the present study, we investigated the ability of MCa to bind to and modify the gating process of cardiac RyR2. By performing pull-down experiments we show that MCa interacts directly with RyR2 with an apparent affinity of 150 nM. By expressing different domains of RyR2 in vitro, we show that MCa binds to two domains of RyR2, which are homologous with those previously identified on RyR1. The effect of MCa binding to RyR2 was then evaluated by three different approaches: (i) [3H]ryanodine binding experiments, showing a very weak effect of MCa (up to 1 μM), (ii) Ca2+ release measurements from cardiac sarcoplasmic reticulum vesicles, showing that MCa up to 1 μM is unable to induce Ca2+ release, and (iii) single-channel recordings, showing that MCa has no effect on the open probability or on the RyR2 channel conductance level. Long-lasting opening events of RyR2 were observed in the presence of MCa only when the ionic current direction was opposite to the physiological direction, i.e. from the cytoplasmic face of RyR2 to its luminal face. Therefore, despite the conserved MCa binding ability of RyR1 and RyR2, functional studies show that, in contrast with what is observed with RyR1, MCa does not affect the gating properties of RyR2. These results highlight a different role of the MCa-binding domains in the gating process of RyR1 and RyR2.
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22

"Scorpio maurus palmatus." CABI Compendium CABI Compendium (January 7, 2022). http://dx.doi.org/10.1079/cabicompendium.64808.

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23

Elrayess, Ranwa A., Mahmoud E. Mohallal, Yomn M. Mobarak, et al. "Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death." Frontiers in Pharmacology 12 (January 10, 2022). http://dx.doi.org/10.3389/fphar.2021.788874.

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Within the last decade, several peptides have been identified according to their ability to inhibit the growth of microbial pathogens. These antimicrobial peptides (AMPs) are a part of the innate immune system of all living organisms. Many studies on their effects on prokaryotic microorganisms have been reported; some of these peptides have cytotoxic properties although the molecular mechanisms underlying their activity on eukaryotic cells remain poorly understood. Smp24 and Smp43 are novel cationic AMPs which were identified from the venom of the Egyptian scorpion Scorpio maurus palmatus. Smp24 and Smp43 showed potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards two acute leukaemia cell lines (myeloid (KG1-a) and lymphoid (CCRF-CEM) leukaemia cell lines) and three non-tumour cell lines CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HaCaT (human skin keratinocytes). Smp24 and Smp43 (4–256 µg/ml) decreased the viability of all cell lines, although HaCaT cells were markedly less sensitive. With the exception HaCaT cells, the caspase-1 gene was uniquely up-regulated in all cell lines studied. However, all cell lines showed an increase in downstream interleukin-1β (IL-1β) expression. Transmission electron microscope studies revealed the formation of cell membrane blebs and the appearance of autolysosomes and lipid droplets in all cell lines; KG1-a leukemia cells also showed the unique appearance of glycogen deposits. Our results reveal a novel mechanism of action for scorpion venom AMPs, activating a cascade of events leading to cell death through a programmed pyroptotic mechanism.
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