INDUCTION OF APOPTOSIS BY CALMODULIN-DEPENDENT INTRACELLULAR CA2+ ELEVATION IN CD4(+) CELLS EXPRESSING GP160 OF HIV

Human CD4(+) cell clones expressing either gp160 or gp120 of HIV-1 und er the transcriptional control of an inducible promoter were used to e xamine the role of Ca2+ signaling in the induction of apoptosis by env elope glycoproteins, Single-cell killing with apoptosis was induced in the cells expressing gp160 while no such apoptosis was found in the c ells expressing gp120. An increase of intracellular Ca2+ was found in the gp160-expressing cells but not in the gp120-expressing cells as de termined by intracellular Ca2+ imaging analysis before the appearance of DNA fragmentation. W7, a calmodulin antagonist, blocked the elevati on of Ca2+ as well as the resultant DNA fragmentation, which thus impl ies that the calmodulin-dependent intracellular Ca2+ release system is first activated by gp160 and thereafter apoptosis takes place. The ab ove results thus indicate that Ca2+ signaling plays a crucial role in the apoptosis accompanying the single-cell death induced by gp160 in C D4(+) cells. (C) 1996 Academic Press, Inc.