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 via the production of hydroxyl radicals. It has been reported to cause both necrotic and apoptotic cell death. The present study was undertaken to evaluate the mode of H2O2-induced cell death and to assess if overexpression of catalase could protect against its toxicity. H2O2 causes cell death of immortalized CSM 14.1 neural cells in a dose-dependent manner. H2O2-induced death was associated with DNA laddering as shown by agarose gel electrophoresis. Stable overexpression of catalase by transfection of a vector containing human cDNA into these cells markedly attenuated H2O2-induced toxic effects. Transfection of a vector containing a SOD cDNA afforded no protection. These results indicate that H2O2 can lead to the activation of endonuclease enzyme that breaks DNA into oligosomes. These cells which overexpress catalase or SOD will help to determine the specific role of H2O2 or O2- in the deleterious effects of a number of toxins.
Mann
H
H
Molecular Neuropsychiatry Section, NIH/NIDA/IRP, Baltimore, MD 21224, USA.
McCoy
M T
MT
Subramaniam
J
J
Van Remmen
H
H
Cadet
J L
JL
D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed / Q000187:drug effects / Q000201:enzymology; D018274:Electroporation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D016877:Oxidants; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase