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A role for oxidative stress and apoptosis on the mechanism of action of catecholamines on oligodendrocyte cell death was next assessed. Catecholamines caused a reduction in intracellular glutathione levels, an accumulation in reactive oxygen species and in heme oxygenase\u20101, the 32 kDa stress\u2010induced protein. All these changes were prevented by N\u2010acetyl\u2010L\u2010cysteine, a thiocompound with antioxidant activity and a precursor of glutathione, and were more pronounced in progenitors than mature cells, which could contribute to their higher susceptibility. Apoptotic cell death, as assessed by activation of caspase\u20109 and \u20133 and cleavage of poly(ADP\u2010ribose) polymerase (a substrate of caspase\u20103), was only observed in oligodendrocyte progenitors. Pretreatment with zVAD, a general caspase inhibitor, prevented activation of caspase\u20109 and \u20103, DNA fragmentation, and decreased progenitors cell death. Furthermore, the expression levels of procaspase\u20103 and the ratio of the proapoptotic protein bax to antiapoptotic protein bcl\u2010xl were several folds higher in immature than mature oligodendrocytes. Taken together, these results strongly suggest that the catecholamine\u2010induced cytotoxicity in oligodendrocytes is developmentally regulated, mediated by oxidative stress, and have characteristics of apoptosis in progenitor cells. GLIA 40:283\u2013299, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10123","type":"journal-article","created":{"date-parts":[[2002,11,6]],"date-time":"2002-11-06T19:01:00Z","timestamp":1036609260000},"page":"283-299","source":"Crossref","is-referenced-by-count":50,"title":["Catecholamine\u2010induced oligodendrocyte cell death in culture is developmentally regulated and involves free radical generation and differential activation of 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