Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/5593
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Type: Journal article
Title: Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways
Author: Movesesyan, V.
Stoica, B.
Yakovlev, A.
Knoblach, S.
Lea, P.
Cernak, I.
Vink, R.
Faden, A.
Citation: Cell Death and Differentiation, 2004; 11(10):1121-1132
Publisher: Nature Publishing Group
Issue Date: 2004
ISSN: 1350-9047
1476-5403
Statement of
Responsibility: 
VA Movsesyan, BA Stoica, AG Yakovlev, SM Knoblach, PM Lea, I Cernak, R Vink and AI Faden.
Abstract: Anandamide (arachidonoylethanolamide or AEA) is an endocannabinoid that acts at vanilloid (VR1) as well as at cannabinoid (CB1/CB2) and NMDA receptors. Here, we show that AEA, in a dose-dependent manner, causes cell death in cultured rat cortical neurons and cerebellar granule cells. Inhibition of CB1, CB2, VR1 or NMDA receptors by selective antagonists did not reduce AEA neurotoxicity. Anandamideinduced neuronal cell loss was associated with increased intracellular Ca2+, nuclear condensation and fragmentation, decreases in mitochondrial membrane potential, translocation of cytochrome c, and upregulation of caspase-3-like activity. However, caspase-3, caspase-8 or caspase-9 inhibitors, or blockade of protein synthesis by cycloheximide did not alter anandamide-related cell death. Moreover, AEA caused cell death in caspase-3-deficient MCF-7 cell line and showed similar cytotoxic effects in caspase-9 dominantnegative, caspase-8 dominant-negative or mock-transfected SH-SY5Y neuroblastoma cells. Anandamide upregulated calpain activity in cortical neurons, as revealed by α-spectrin cleavage, which was attenuated by the calpain inhibitor calpastatin. Calpain inhibition significantly limited anandamide- induced neuronal loss and associated cytochrome c release. These data indicate that AEA neurotoxicity appears not to be mediated by CB1, CB2, VR1 or NMDA receptors and suggest that calpain activation, rather than intrinsic or extrinsic caspase pathways, may play a critical role in anandamide-induced cell death.
Keywords: Arachidonoylethanolamide; calpain; caspase; neuronal death; cortical neurons; cerebellar granule cells
Rights: © 2004 Nature Publishing Group
RMID: 0020041482
DOI: 10.1038/sj.cdd.4401442
Published version: http://www.nature.com/cdd/journal/v11/n10/abs/4401442a.html
Appears in Collections:Pathology publications

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