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

Anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor l igand has been suggested to have physiological role in mammalian nervous sy stem. However, little is known about the role of anandamide on neuronal cel ls, Here, we demonstrate that anandamide causes death of PC-12 cells, shoei ng 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-acet yl cysteine prevented anandamide-induced superoxide anion formation and cel l death, implying that intracellular superoxide is a novel mediator of anan damide-induced apoptosis of PC-12 cells, (C) 2000 Federation of European Bi ochemical Societies.