Abstract #3091

Gottschalk S, Chan T, Raymond V, Bilodeau M, Leibfritz D, Zwingmann C

To clarify whether changes in glucose metabolism occur prior to the already known events in the apoptotic process, and whether these can be prevented by the immunosuppressant Cyclosporine A (CsA), we used multinuclear NMR spectroscopy and molecular studies to characterize metabolic pathways in mice liver during anti-Fas-induced apoptosis. An upregulation of specific metabolic pathways of glucose was the earliest indicator of the effect of Fas on the liver. CsA prevented apoptosis and energy failure at late stages, while the reversal of Fas-induced metabolic upregulation at early stages preceded the protective effect of EGF on programmed cell death. These phenomena provide useful hints for the understanding of early mechanisms controlling apoptotic cell death.