Kinetics of hydrogen peroxide elimination by astrocytes and C6 glioma cells

Oxidative stress is implicated in a variety of disorders including neurodegenerative diseases, and H2O2 is important in the generation of reactive oxygen and oxidative stress. In this study, we have examined the rate of extracellular H2O2 elimination and relevant enzyme activities in cultured astrocytes and C6 glioma cells and have analyzed the results based on a mathematical model. As compared with other types of cultured cells, astrocytes showed higher activity of glutathione peroxidase (GPx) but lower activities for GSH recycling. C6 cells showed relatively low GPx activity, and treatment of C6 cells with dibutyryl-cAMP, which induces astrocytic differentiation, increased catalase activity and H2O2 permeation rate but exerted little effect on other enzyme activities. A mathematical model [N. Makino, K. Sasaki, N. Hashida, Y. Sakakura, A metabolic model describing the H2O2 elimination by mammalian cells including H2O2 permeation through cytoplasmic and peroxisomal membranes: comparison with experimental data, Biochim. Biophys. Acta 1673 (2004) 149-159.], which includes relevant enzymes and H2O2 permeation through membranes, was found to be fitted well to the H2O2 concentration dependences of removal reaction with the permeation rate constants as variable parameters. As compared with PC12 cells as a culture model for neuron, H2O2 removal activity of astrocytes was considerably higher at physiological H2O2 concentrations. The details of the mathematical model are presented in Appendix.