1. Department of Neurology and Program in Neurobiology, State University of New York at Stony Brook, U.S.A.
2. ^*Apoptosis and Cell Death Research Program, The Burnham Institute, La Jolla, California, U.S.A.

Correspondence: Francis J Antonawich, Department of Neurology, HSC T12 020, SUNY at Stony Brook, Stony Brook, NY 11794-8121, U.S.A.

Received 25 September 1997; Revised 27 November 1997; Accepted 2 December 1997.

Abstract

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.