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From the Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, D-78457 Konstanz, Germany

Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.

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• Manabat, C., Han, B.H., Wendland, M., Derugin, N., Fox, C.K., Choi, J., Holtzman, D.M., Ferriero, D.M., Vexler, Z.S. (2003). Reperfusion Differentially Induces Caspase-3 Activation in Ischemic Core and Penumbra After Stroke in Immature Brain. Stroke 34: 207-213 [Abstract] [Full Text]  
• Chandra, D., Liu, J.-W., Tang, D. G. (2002). Early Mitochondrial Activation and Cytochrome c Up-regulation during Apoptosis. J. Biol. Chem. 277: 50842-50854 [Abstract] [Full Text]  
• Terminella, C., Tollefson, K., Kroczynski, J., Pelli, J., Cutaia, M. (2002). Inhibition of apoptosis in pulmonary endothelial cells by altered pH, mitochondrial function, and ATP supply. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L1291-L1302 [Abstract] [Full Text]  
• Obrero, M., Yu, D. V., Shapiro, D. J. (2002). Estrogen Receptor-dependent and Estrogen Receptor-independent Pathways for Tamoxifen and 4-Hydroxytamoxifen-induced Programmed Cell Death. J. Biol. Chem. 277: 45695-45703 [Abstract] [Full Text]  
• Duan, L., Gan, H., Golan, D. E., Remold, H. G. (2002). Critical Role of Mitochondrial Damage in Determining Outcome of Macrophage Infection with Mycobacterium tuberculosis. J. Immunol. 169: 5181-5187 [Abstract] [Full Text]  
• Zou, Z., Sasaguri, S., Rajesh, K. G., Suzuki, R. (2002). dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts. Am. J. Physiol. Heart Circ. Physiol. 283: H1968-H1974 [Abstract] [Full Text]  

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