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Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells

ARAN - Access to Research at NUI Galway

Show simple item record Mnich, Katarzyna en Finn, David P. en Dowd, Eilis en Gorman, Adrienne M. en 2010-08-20T10:32:04Z en 2010-08-20T10:32:04Z en 2010 en
dc.identifier.citation Mnich, K., Finn, D., Dowd, E., & Gorman, A. (2010) Inhibition by anandamide of 6-hydroxydopamine-induced cell death in PC12 cells. Int J Cell Biol, 2010, 818497. en
dc.identifier.uri en
dc.description.abstract 6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson's disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB1 or CB2) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA. en
dc.format application/pdf en
dc.language.iso en en
dc.subject Pharmacology en
dc.title Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells en
dc.type Article en
dc.local.publishedsource en
dc.description.peer-reviewed peer-reviewed en
dc.contributor.funder Irish Research Council for Science Engineering and Technology en
dc.contributor.funder Science Foundation Ireland en

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