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  • Title: Specific inhibitors of vacuolar type H(+)-ATPases induce apoptotic cell death.
    Author: Nishihara T, Akifusa S, Koseki T, Kato S, Muro M, Hanada N.
    Journal: Biochem Biophys Res Commun; 1995 Jul 06; 212(1):255-62. PubMed ID: 7612014.
    Abstract:
    Concanamycin A and bafilomycin A1 are known as strong inhibitors of the vacuolar type H(+)-ATPases in vitro. These inhibitors exhibited cytotoxic 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 A1 induce a significant increase in the proportion of fragmented DNA in agarose gel electrophoresis. Flow cytometric cell cycle analysis of WEHI 231 cells stimulated with concanamycin A revealed the increased percentage of apoptotic cells with hypodiploid DNA. These findings indicate that cell death induced by specific inhibitors of vacuolar type H(+)-ATPases occurs through apoptosis.
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