A ROLE OF PEROXIDES IN CA2-INDUCED APOPTOSIS IN CULTURED RAT CORTICAL-NEURONS( IONOPHORE)

The implication of reactive oxygen species for the Ca2+ ionophore iono mycin-induced apoptosis was investigated in cultured cortical neurons from embryonic rats. Ionomycin increased the production of intracellul ar peroxides as measured by flow cytometric analysis with 6-carboxy-2' 7'-dichlorodihydrofluorescein diacetate, di(acetoxymethyl ester). Low doses of ionomycin increased the level of manganese-superoxide dismuta se (Mn-SOD). In addition, N-acetyl-L-cysteine prevented apoptotic neur onal death induced by ionomycin in a dose-dependent manner. Buthionine sulfoximine suppressed the effect of N-acetyl-L-cysteine. These resul ts suggest that peroxides and redox-regulation play an important role in the apoptosis of neurons induced by elevation of intracellular Ca2 concentration. (C) 1996 Academic Press, Inc.