Bcl-x(l) Bax interaction after transient global ischemia.
Five minutes of bilateral common carotid artery occlusion in the Mongolian gerbil results in a selective, delayed death of CA1 pyramidal neurons. Although Bcl-2 appears to protect a variety of cells from cell death, the precise role of this apoptosis-regulating protein is complicated. We used immunoblots to estimate levels of Bcl-2, Bcl-x(l), and Bax at various times after carotid occlusion. Rather than Bcl-2, Bcl-x(l) appears to be the predominant neuroprotective form of this family of proto-oncogenes in the gerbil hippocampus. After transient ischemia, Bcl-2 and Bcl-x(l) protein levels remained the same. However, Bax levels were dramatically increased at 6 hours after ischemia, compared with sham-operated animals, and were still elevated at 72 hours after ischemia. To monitor dimerization interactions among theses apoptosis-regulating molecules, immunoprecipitation studies were conducted. These studies demonstrated that Bcl-x(l) association with Bax increases after ischemia. Therefore, Bax may disrupt the more favorable Bcl-x(l) (Bcl-2) interactions necessary for normal neuronal functioning and thus promote transient ischemic death.
Department of Neurology and Program in Neurobiology, State University of New York at Stony Brook, 11794-8121, USA.
F J
FJ
Antonawich
S
S
Krajewski
J C
JC
Reed
J N
JN
Davis
D000818:Animals; D017209:Apoptosis; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein