SPECIFIC INHIBITORS OF VACUOLAR-TYPE H-ATPASES INDUCE APOPTOTIC CELL-DEATH()

Concanamycin A and bafilomycin A1 are known as strong inhibitors of th e vacuolar type H+-ATPases in vitro. These inhibitors exhibited cytoto xic effects on twelve cell lines in cell viability assay. On the other hand, the F1F0-type H+-ATPase inhibitor oligomycin and the E1E2-type H+-ATPase inhibitor vanadate showed no cytotoxic effect. We show here that concanamycin A and bafilomycin Al induce a significant increase i n the proportion of fragmented DNA in agarose get electrophoresis. Flo w cytometric cell cycle analysis of WEHI 231 cells stimulated with con canamycin A revealed the increased percentage of apoptotic cells with hypodiploid DNA. These findings indicate that cell death induced by sp ecific inhibitors of vacuolar type H+-ATPases occurs through apoptosis . (C) 1995 Academic Press, Inc.