Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells
Mnich, Katarzyna Finn, David P. Dowd, Eilis Gorman, Adrienne M.
Mnich, Katarzyna
Finn, David P.
Dowd, Eilis
Gorman, Adrienne M.
Loading...
Publication Date
2010
Keywords
Type
Article
Downloads
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.
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.
Publisher
Publisher DOI
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland