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Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced cytotoxicity by activating the Akt signaling pathway and increasing glutathione peroxidase expression
dc.contributor.author | Fernandez Gomez, Francisco Jose | |
dc.contributor.author | Pastor, MD | |
dc.contributor.author | Garcia-Martinez, Eva Maria | |
dc.contributor.author | Melero Fernandez de Mera, Raquel Maria | |
dc.contributor.author | Gou-Fabregas, M | |
dc.contributor.author | Gomez-Lazaro, Maria | |
dc.contributor.author | Calvo, Soledad | |
dc.contributor.author | Soler, R | |
dc.contributor.author | Galindo, Maria F | |
dc.contributor.author | Jordan, Joaquin | |
dc.date.accessioned | 2024-02-05T18:40:41Z | |
dc.date.available | 2024-02-05T18:40:41Z | |
dc.date.issued | 2006 | |
dc.identifier.citation | Fernandez-Gomez FJ, Pastor MD, Garcia-Martinez EM, Melero-Fernandez de Mera R, Gou-Fabregas M, Gomez-Lazaro M, Calvo S, Soler RM, Galindo MF, Jordán J. Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced cytotoxicity by activating the Akt signaling pathway and increasing glutathione peroxidase expression. Neurobiol Dis. 2006 Nov;24(2):296-307. doi: 10.1016/j.nbd.2006.07.005. Epub 2006 Sep 15. PMID: 16978869. | es |
dc.identifier.issn | 0969-9961 | |
dc.identifier.other | https://pubmed.ncbi.nlm.nih.gov/16978869/ | es |
dc.identifier.uri | http://hdl.handle.net/20.500.12020/1209 | |
dc.description.abstract | Parkinson disease (PD) is the second-most common age-related neurodegenerative disease and is characterized by the selective destruction of dopaminergic neurons. Increasing evidence indicates that oxidative stress plays a crucial role in the pathogenesis of idiopathic PD. Anti-oxidant agents including catalase, manganese porphyrin and pyruvate confer cytoprotection to different cell cultures when challenged with 6-hydroxydopamine (6-OHDA). Herein we used rat cerebellar granular cell cultures to ascertain the plausible cellular pathways involved in pyruvate-induced cytoprotection against 0.1 mM 6-OHDA. Pyruvate provided cytoprotection in a concentration-dependent manner (2-10 mM). Consistent with its well-established anti-oxidant capacity, pyruvate (10 mM) prevented 6-OHDA-induced lipid peroxidation by blocking the rise in intracellular peroxides and maintaining the intracellular reduced glutathione (GSH) levels. Further experiments revealed that pyruvate increased Akt, but not extracellular signal-regulated kinase phosphorylation. Moreover, phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated pyruvate-induced cytoprotection indicating that PI3K-mediated Akt activation is necessary for pyruvate to induce cytoprotection. On the other hand, pyruvate also up-regulated glutathione peroxidase mRNA levels, but not those of the anti-oxidant enzymes superoxide dismutase-1 and -2, catalase or the anti-apoptotic oncogenes Bcl-2 or Bcl-xL. In summary, our results strongly suggest that pyruvate, besides the anti-oxidant properties related to its structure, exerts cytoprotective actions by activating different anti-apoptotic routes that include gene regulation and Akt pathway activation | es |
dc.language.iso | en | es |
dc.publisher | Elsevier | es |
dc.title | Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced cytotoxicity by activating the Akt signaling pathway and increasing glutathione peroxidase expression | es |
dc.type | article | es |
dc.identifier.doi | 10.3390/ijms242115812 | |
dc.issue.number | 2 | es |
dc.journal.title | Neurobiology of Disease | es |
dc.page.initial | 296 | es |
dc.page.final | 307 | es |
dc.rights.accessRights | embargoedAccess | es |
dc.subject.area | Biología Celular y Molecular | es |
dc.subject.area | Ciencias Biomédicas | es |
dc.subject.keyword | catalase | es |
dc.subject.keyword | opper zinc superoxide dismutase | es |
dc.subject.keyword | glutathione | es |
dc.subject.keyword | glutathione peroxidase | es |
dc.subject.keyword | mitogen activated protein kinase | es |
dc.subject.keyword | peroxide | es |
dc.subject.keyword | cytotoxicity | es |
dc.subject.keyword | granular cell | es |
dc.subject.keyword | lipid peroxidation | es |
dc.volume.number | 24 | es |
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