Glutathione Peroxidase-Catalase Cooperativity Is Required for Resistance to Hydrogen Peroxide by Mature Rat Oligodendrocytes

Author:

Baud Olivier,Greene Amanda E.,Li Jianrong,Wang Hong,Volpe Joseph J.,Rosenberg Paul A.

Abstract

Oxidative mechanisms of injury are important in many neurological disorders, including hypoxic-ischemic brain damage. Cerebral palsy after preterm birth is hypothesized to be caused by hypoxic-ischemic injury of developing oligodendrocytes (OLs). Here we examined the developmental sensitivity of OLs to exogenous hydrogen peroxide (H2O2) with stage-specific rat oligodendrocyte cultures. We found that H2O2itself or that generated by glucose oxidase was more toxic to developing than to mature OLs. Mature OLs were able to degrade H2O2faster than developing OLs, suggesting that higher antioxidant enzyme activity might be the basis for their resistance. Catalase expression and activity were relatively constant during oligodendrocyte maturation, whereas glutathione peroxidase (GPx) was upregulated with a twofold to threefold increase in its expression and activity. Thus, it appeared that the developmental change in resistance to H2O2was caused by modulation of GPx but not by catalase expression. To test the relative roles of catalase and GPx in the setting of oxidative stress, we measured enzyme activity in cells exposed to H2O2and found that H2O2induced a decrease in catalase activity in developing but not in mature OLs. Inhibition of GPx by mercaptosuccinate led to an increase in the vulnerability of mature OLs to H2O2as well as a reduction in catalase activity. Finally, H2O2-dependent inactivation of catalase in developing OLs was prevented by the GPx mimic ebselen. These data provide evidence for a key role for GPx-catalase cooperativity in the resistance of mature OLs to H2O2-induced cell death.

Publisher

Society for Neuroscience

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