OVEREXPRESSION OF SUPEROXIDE-DISMUTASE AND CATALASE IN IMMORTALIZED NEURAL CELLS - TOXIC EFFECTS OF HYDROGEN-PEROXIDE

Hydrogen peroxide (H2O2) is a known toxicant which causes its damage v ia the production of hydroxyl radicals. It has been reported to cause both necrotic and apoptotic cell death. The present study was undertak en to evaluate the mode of H2O2-induced cell death and to assess if ov erexpression of catalase could protect against its toxicity. H2O2 caus es cell death of immortalized CSM 14.1 neural cells in a dose-dependen t manner. H2O2-induced death was associated with DNA laddering as show n by agarose gel electrophoresis. Stable overexpression of catalase by transfection of a vector containing human cDNA into these cells marke dly attenuated H2O2-induced toxic effects. Transfection of a vector co ntaining a SOD cDNA afforded no protection. These results indicate tha t H2O2 can lead to the activation of endonuclease enzyme that breaks D NA into oligosomes. These cells which overexpress catalase or SOD will help to determine the specific role of H2O2 or O-2(radical anion) in the deleterious effects of a number of toxins. (C) 1997 Elsevier Scien ce B.V.