Specific Inhibitors of Vacuolar Type H+-ATPases Induce Apoptotic Cell Death

Tatsuji Nishihara, Sumio Akifusa, Takeyoshi Koseki, Satsuki Kato, Miyuki Muro, Nobuhiro Hanada

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)255-262
Number of pages8
JournalBiochemical and biophysical research communications
Volume212
Issue number1
DOIs
Publication statusPublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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