RRC ID 1207
Author Hashida K, Sakakura Y, Makino N.
Title Kinetic studies on the hydrogen peroxide elimination by cultured PC12 cells: rate limitation by glucose-6-phosphate dehydrogenase.
Journal Biochim Biophys Acta
Abstract Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and brain ischemia, and hydrogen peroxide (H(2)O(2)) plays a central role in the stress. In this study, we have examined the kinetics of H(2)O(2) elimination by PC12 cells as a neuronal model in connection with the enzyme activities supporting the reaction. Similarly to other cell lines previously studied, H(2)O(2) removal kinetics could be divided into two reactions: one apparently following the Michaelis-Menten kinetics (GSH-dependent reaction) and the other following the first-order kinetics (mainly catalyzed by catalase). Based on the enzyme activities in the cell homogenate, it was inferred that glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the GSH- and NADPH-dependent H(2)O(2) elimination by PC12 cells. This is in contrast with fibroblasts and endothelial cells previously examined, in which glutathione reductase (GR) is rate-limiting in the reaction sequence. Treatment of PC12 cells with nerve growth factor increased G6PD activity in the cell homogenate and H(2)O(2) removal activity of the whole cells, with a concomitant increase in the resistance against H(2)O(2) toxicity. These results suggest the importance of G6PD in the antioxidant function of brain and pathogenesis of the oxidative stress-related diseases.
Volume 1572(1)
Pages 85-90
Published 2002-8-15
DOI 10.1016/s0304-4165(02)00282-9
PII S0304416502002829
PMID 12204336
MeSH Animals Catalase / metabolism Cell Survival Cells, Cultured Dose-Response Relationship, Drug Glucosephosphate Dehydrogenase / chemistry Glucosephosphate Dehydrogenase / metabolism* Glutathione Peroxidase / metabolism Glutathione Reductase / metabolism Hydrogen Peroxide / analysis Hydrogen Peroxide / metabolism* Hydrogen Peroxide / toxicity Kinetics PC12 Cells / chemistry PC12 Cells / drug effects PC12 Cells / metabolism* Rats
IF 3.411
Times Cited 25
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells PC-12(RCB0009)