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Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mitochondrial cytochrome c release and apoptosis in response to malonate
dc.contributor.author | Gómez-Lazaro, María | |
dc.contributor.author | Galindo, María Francisca | |
dc.contributor.author | Melero Fernández de Mera, Raquel María | |
dc.contributor.author | Fernández Gómez, Francisco José | |
dc.contributor.author | Cancannon, CG | |
dc.contributor.author | Segura, Miguel | |
dc.contributor.author | Comella, Joan X | |
dc.contributor.author | Prehn, J H M | |
dc.contributor.author | Jordan, Joaquin | |
dc.date.accessioned | 2024-02-02T15:54:15Z | |
dc.date.available | 2024-02-02T15:54:15Z | |
dc.date.issued | 2007 | |
dc.identifier.citation | Gómez-Lazaro, M., Galindo, M. F., Melero-Fernández de Mera, R. M., Fernandez-Gómez, F. J., Concannon, C. G., Segura, M. F., Comella, J. X., Prehn, J. H. M., & Jordan, J. (2007). Reactive Oxygen Species and p38 Mitogen-Activated Protein Kinase Activate Bax to Induce Mitochondrial Cytochrome c Release and Apoptosis in Response to Malonate. Molecular Pharmacology, 71(3), 736-743. https://doi.org/10.1124/mol.106.030718 | es |
dc.identifier.issn | 15210111 | |
dc.identifier.other | https://pubmed.ncbi.nlm.nih.gov/17172466/ | es |
dc.identifier.uri | http://hdl.handle.net/20.500.12020/1157 | |
dc.description.abstract | Malonate, an inhibitor of mitochondrial complex II, is a widely used toxin to study neurodegeneration in Huntington's disease and ischemic stroke. We have shown previously that malonate increased reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells, leading to oxidative stress, cytochrome c release, and apoptotic cell death. Expression of a green fluorescent protein-Bax fusion protein in SH-SY5Y neuroblastoma cells demonstrated a Bax redistribution from the cytosol to mitochondria after 12 to 24 h of malonate treatment that coincided with mitochondrial potential collapse and chromatin condensation. Inhibition of Bax translocation using furosemide, as well as Bax gene deletion, afforded significant protection against malonate-induced apoptosis. Further experiments revealed that malonate induced a prominent increase in the level of activated p38 mitogen-activated protein (MAP) kinase and that treatment with the p38 MAP kinase inhibitor SKF86002 potently blocked malonate-induced Bax translocation and apoptosis. Treatment with vitamin E diminished ROS production, reduced the activation status of p38 MAP kinase, inhibited Bax translocation, and protected against malonate-induced apoptosis. Our data suggest that malonate-induced ROS production and subsequent p38 MAP kinase activation mediates the activation of the pro-apoptotic Bax protein to induce mitochondrial membrane permeabilization and neuronal apoptosis. | es |
dc.language.iso | en | es |
dc.publisher | American Society for Pharmacology and Experimental Therapeutics | es |
dc.title | Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mitochondrial cytochrome c release and apoptosis in response to malonate | es |
dc.type | article | es |
dc.identifier.doi | https://doi.org/10.1124/mol.106.030718 | |
dc.issue.number | 3 | es |
dc.journal.title | Molecular Pharmacology | es |
dc.page.initial | 1 | es |
dc.page.final | 8 | es |
dc.rights.accessRights | embargoedAccess | es |
dc.subject.area | Biología Celular y Molecular | es |
dc.subject.area | Ciencias Biomédicas | es |
dc.subject.keyword | Animals | es |
dc.subject.keyword | Cells, Cultured | es |
dc.subject.keyword | Protein Transport / drug effects | es |
dc.subject.keyword | Reactive Oxygen Species | es |
dc.subject.keyword | Malonates / pharmacology | es |
dc.subject.unesco | 32 Ciencias Médicas | es |
dc.volume.number | 71 | es |
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