Translocation of cytochrome c following transient global ischemia in the gerbil

Abstract

Five minutes of transient global ischemia results in the delayed neuronal death of CA1 hippocampal cells. These pyramidal cells follow an apoptotic cell death cascade of events, initiated by the activation of the bcl-2 family of regulatory proteins and ending with caspase activation. The mitochondrial protein cytochrome c has been demonstrated to activate the precursor forms of caspase to their active forms. This is under the control of the bcl-2 protein family. The present study examined the accumulation of cytosolic cytochrome c following transient ischemia. At 72 h post-carotid artery occlusion there was a translocation of cytochrome c from the mitochondria to the cytoplasm just prior to the onset of cell death. By 7 days, when CA1 cell death is complete, there was no longer a significant difference between control and ischemic tissue. Therefore, cytochrome c appears to be a vital component in the apoptotic sequence of events following global ischemia.