Bibliographic Details
| Title: |
Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model |
| Authors: |
Satish Kumar, Miriam Aceves, Jose Granados, Lorena Guerra, Felicia Juarez, Earl Novilla, Ana C. Leandro, Marcelo Leandro, Juan Peralta, Sarah Williams-Blangero, Elda E. Sanchez, Jacob A. Galan, John Blangero, Joanne E. Curran |
| Source: |
Biomolecules, Vol 15, Iss 3, p 381 (2025) |
| Publisher Information: |
MDPI AG, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Microbiology |
| Subject Terms: |
human iPSCs, NSCs, Mojave rattlesnake venom, neurocellular response, molecular mechanisms, Microbiology, QR1-502 |
| More Details: |
The Mojave rattlesnake venom shows significant geographical variability. The venom of Type A animals primarily contains β-neurotoxin referred to as Mojave Toxin (MTX), which makes bites from this snake particularly feared. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave Type A rattlesnake venom using induced pluripotent stem cell-derived neural stem cells to unveil the molecular mechanisms underlying the damage caused by this snake’s envenomation. Our results suggest that snake venom metalloproteases, although having a limited repertoire in Type A venom, facilitate venom spread by digesting the tissue’s extracellular matrix. The MTX, which is composed of heterodimers of basic and acidic phospholipase-A2, co-opts the host arachidonic acid and Ca2+ second messenger mechanisms and triggers multiple signaling cascades, such as the activation of MAPKs and NF-κB-regulated proinflammatory genes; the neurotransmitter overload in excitatory synapses leading to a presynaptic blockade of nerve signals; and the upregulation of unfolded protein response (UPR) due to the depletion of Ca2+ from the endoplasmic reticulum. The upregulated UPR and the oxidative stress caused by reactive oxygen species generated in cytochromeP4501A1-mediated hydroxylation of arachidonic acid contribute to mitochondrial toxicity. The activation of UPR, mitochondrial toxicity, and oxidative stress synergistically contributed to apoptotic and ferroptotic cell death. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2218-273X |
| Relation: |
https://www.mdpi.com/2218-273X/15/3/381; https://doaj.org/toc/2218-273X |
| DOI: |
10.3390/biom15030381 |
| Access URL: |
https://doaj.org/article/20bc1e57be8348f0b6bb31104a0b2d39 |
| Accession Number: |
edsdoj.20bc1e57be8348f0b6bb31104a0b2d39 |
| Database: |
Directory of Open Access Journals |
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