Mechanism of A23187-induced apoptosis in HL-60 cells: Dependency on mitochondrial permeability transition but not on NADPH oxidase

Noriko Kajitani, Hirotsugu Kobuchi, Hirofumi Fujita, Hiromi Yano, Takuzo Fujiwara, Tatsuji Yasuda, Kozo Utsumi

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19 Citations (Scopus)


Calcium ions (Ca2+) are involved in a number of physiological cellular functions including apoptosis. An elevation in intracellular levels of Ca2+ in A23187-treated HL-60 cells was associated with the generation of both intracellular and extracellular reactive oxygen species (ROS) and induction of apoptotic cell death. A23187-induced apoptosis was prevented by cyclosporin A, a potent inhibitor of mitochondrial permeability transition (MPT). The generation of extracellular ROS was suppressed by the NADPH oxidase inhibitor diphenylene iodonium, and by superoxide dismutase, but these agents had no effect on A23187-induced apoptosis. In contrast, the blocking of intracellular ROS by a cell-permeant antioxidant diminished completely the induction of MPT and apoptosis. In isolated mitochondria, the addition of Ca2+ induced a typical MPT concomitant with the generation of ROS, which leads to augmentation of intracellular ROS levels. These results indicate that intracellular not extracellular ROS generated by A23187 is associated with the opening of MPT pores that leads to apoptotic cell death.

Original languageEnglish
Pages (from-to)2701-2711
Number of pages11
JournalBioscience, Biotechnology and Biochemistry
Issue number11
Publication statusPublished - Nov 30 2007



  • Apoptosis
  • Calcium
  • Mitochondrial permeability transition
  • NADPH oxidase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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