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The goal of the present study was to elucidate the effects of APPsw on mechanisms of apoptotic cell death. Therefore, PC12 cells were stably transfected with human APPsw. Here we report that the vulnerability of APPsw\u2010bearing PC12 cells to undergo apoptotic cell death was significantly enhanced after exposure to hydrogen peroxide compared to human wild\u2010type APP\u2010bearing cells, empty vector\u2010transfected cells, and parent untransfected cells. In addition, we have analyzed the potential influence of several mechanisms that can interfere with the execution of the apoptotic cell death program: the inhibition of cell death by the use of caspase inhibitors and the reduction of oxidative stress by the use of (\u00b1)\u2010\u03b1\u2010tocopherol (vitamin E). Interestingly, oxidative stress\u2010induced cell death was significantly attenuated in APPsw PC12 cells by pretreatment with caspase\u20103 inhibitors but not with caspase\u20101 inhibitors. In parallel, caspase\u20103 activity was markedly elevated in APPsw PC12 after stimulation with hydrogen peroxide for 6 hr, whereas caspase\u20101 activity was unaltered. In addition, oxidative stress\u2010induced cell death could be reduced after pretreatment of APPsw cells with (\u00b1)\u2010\u03b1\u2010tocopherol. The protective potency of (\u00b1)\u2010\u03b1\u2010tocopherol was even greater than that of caspase\u20103 inhibitors. Our findings further emphasize the role of mutations in the amyloid precursor protein in apoptotic cell death and may provide the fundamental basis for further efforts to elucidate the underlying processes caused by FAD\u2010related mutations. J. Neurosci. Res. 64:183\u2013192, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.1064","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T17:30:12Z","timestamp":1030296612000},"page":"183-192","source":"Crossref","is-referenced-by-count":82,"title":["Elevated vulnerability to oxidative stress\u2010induced cell death and activation of caspase\u20103 by the Swedish amyloid precursor protein 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