Function of BID - a molecule of the bcl-2 family - in ischemic cell death in the brain

Mitochondrial mechanisms, particularly the release of cytochrome c,
play a role in the death of nerve and glial cells in cerebral
ischemia. We have currently investigated whether BID, a
proapoptotic molecule of the bcl-2 family and promoter of the
release of cytochrome c is expressed in the brain, activated by
cerebral ischemia in vivo, and contributes to ischemic cell death.
We found BID in the cytosol of mouse brain and of primary cultured
mouse neurons and showed that neuronal BID is a substrate for
caspase 8. BID was cleaved in vivo 4 h after transitory occlusion
of the middle cerebral artery. Further, BID-/- mice had a
significant attenuation of infarction (-67%) and significantly
lower release of cytochrome c (-41 %). The findings indicate that
the proapoptotic molecule BID may contribute to the demise of nerve
cells from cerebral ischemia by release of cytochrome c and
activation of caspase. Copyright (C) 2002 S. Karger AG, Basel.