Transient cerebral ischemia induces delayed proapoptotic Bad translocation to mitochondria in CA1 sector of hippocampus.
Delayed ischemic brain damage is associated with mitochondrial dysfunction, but the underlying mechanisms are not known in detail. Recent data suggest that the process is associated with multidirectional changes in the activities of various proteins located in mitochondria. Of these, the stress-activated kinase JNK is delay-activated postischemia. We induced 5 min cerebral ischemia in gerbils followed by 3, 24, 48, 72 and 96 h of reperfusion. Here we show the postischemic translocation of proapoptotic protein Bad to mitochondria. Immunoelectron microscopic examination revealed the co-appearance of Bad and Bcl-2 proteins in postischemic mitochondria in ischemia-vulnerable CA1 sector of hippocampus as opposed to the ischemia-resistant DG region. Mitochondrial increase of Bad protein is coincident with a transient decrease of the active, phosphorylated form of prosurvival kinase, Raf-1, under conditions of long reperfusion. The above demonstrated sequence of events is likely to play a role in delayed postischemic nerve cell death.
Dłuzniewska
Joanna
J
Molecular Biology Unit, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
Beresewicz
Małgorzata
M
Wojewódzka
Urszula
U
Gajkowska
Barbara
B
Zabłocka
Barbara
B
D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015424:Reperfusion / Q000379:methods; D013997:Time Factors; D051025:bcl-Associated Death Protein
D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D019908:Proto-Oncogene Proteins c-raf