Authors: Gavin C Higgins Philip M Beart Phillip Nagley
Publish Date: 2009/07/07
Volume: 66, Issue: 16, Pages: 2773-2787
Abstract
To characterize neuronal death primary cortical neurons C57/Black 6 J mice were exposed to hydrogen peroxide H2O2 and staurosporine Both caused cell shrinkage nuclear condensation DNA fragmentation and loss of plasma membrane integrity Neither treatment induced caspase7 activity but caspase3 was activated by staurosporine but not H2O2 Each treatment caused redistribution from mitochondria of both endonuclease G Endo G and cytochrome c Neurons knocked down for Endo G expression using siRNA showed reduction in both nuclear condensation and DNA fragmentation after treatment with H2O2 but not staurosporine Endo G suppression protected cells against H2O2induced cell death while staurosporineinduced death was merely delayed We conclude that staurosporine induces apoptosis in these neurons but severe oxidative stress leads to Endo Gdependent death in the absence of caspase activation programmed cell deathtype III Therefore oxidative stress triggers in neurons a form of necrosis that is a systematic cellular response subject to molecular regulation
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