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.
Plesnila
Nikolaus
N
Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. plesnila@icf.med.uni-muenchen.de
Zinkel
Sandra
S
Amin-Hanjani
Sepideh
S
Qiu
Jianhua
J
Korsmeyer
Stanley J
SJ
Moskowitz
Michael A
MA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; C494816:Bid protein, rat; D002352:Carrier Proteins; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2