BCL-X(1) BAX INTERACTION AFTER TRANSIENT GLOBAL-ISCHEMIA

Five minutes of bilateral common carotid artery occlusion in the Mongo lian gerbil results in a selective, delayed death of CA1 pyramidal neu rons. Although Bcl-2 appears to protect a variety of cells from cell d eath, the precise role of this apoptosis-regulating protein is complic ated. We used immunoblots to estimate levels of Bcl-2, Bcl-x(1), and B ax at various times after carotid occlusion. Rather than Bcl-2, Bcl-x( 1) appears to be the predominant neuroprotective form of this family o f proto-oncogenes in the gerbil hippocampus. After transient ischemia, Bcl-2 and Bcl-x(1) protein levels remained the same. However, Bax lev els were dramatically increased at 6 hours after ischemia, compared wi th sham-operated animals, and were still elevated at 72 hours after is chemia. To monitor dimerization interactions among theses apoptosis-re gulating molecules? immunoprecipitation studies were conducted. These studies demonstrated that Bcl-x(1) association with Bax increases afte r ischemia. Therefore, Bax may disrupt the more favorable Bcl-x(1) (Bc l-2) interactions necessary for normal neuronal functioning and thus p romote transient ischemic death.