Anandamide induces apoptosis of PC-12 cells: involvement of superoxide and caspase-3

Anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor ligand has been suggested to have physiological role in mammalian nervous system. However, little is known about the role of anandamide on neuronal cells. Here, we demonstrate that anandamide causes death of PC-12 cells, showi...

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Bibliographic Details
Published in:FEBS letters 2000-04, Vol.472 (1), p.39-44
Main Authors: Sarker, Krishna Pada, Obara, Soichi, Nakata, Masanori, Kitajima, Isao, Maruyama, Ikuro
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Anandamide
Animals
Apoptosis
Apoptosis - physiology
Arachidonic Acids - antagonists & inhibitors
Arachidonic Acids - pharmacology
Arachidonic Acids - physiology
Caspase 3
Caspases - metabolism
Cell Survival
CPP32-like protease
Endocannabinoids
PC-12 cell
PC12 Cells
Polyunsaturated Alkamides
Rats
Superoxide
Superoxides - metabolism
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Summary:Anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor ligand has been suggested to have physiological role in mammalian nervous system. However, little is known about the role of anandamide on neuronal cells. Here, we demonstrate that anandamide causes death of PC-12 cells, showing marked DNA condensation and fragmentation, appearance of cells at sub-G 0/G 1 and redistribution of phosphatidyl serine, the hallmark features of apoptosis. Anandamide raised intracellular superoxide level and CPP32-like protease activity in PC-12 cells markedly. Furthermore, antioxidant N-acetyl cysteine prevented anandamide-induced superoxide anion formation and cell death, implying that intracellular superoxide is a novel mediator of anandamide-induced apoptosis of PC-12 cells.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(00)01425-3