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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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
Volume71
Issue number11
DOIs
Publication statusPublished - 2007

Fingerprint

NADPH Oxidase
HL-60 Cells
Calcimycin
Cell death
reactive oxygen species
Permeability
Reactive Oxygen Species
permeability
apoptosis
Apoptosis
Oxygen
calcium
cells
cell death
Cell Death
Mitochondria
cyclosporine
Antioxidants
Cyclosporine
Superoxide Dismutase

Keywords

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

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry (miscellaneous)
  • Applied Microbiology and Biotechnology
  • Food Science

Cite this

Mechanism of A23187-induced apoptosis in HL-60 cells : Dependency on mitochondrial permeability transition but not on NADPH oxidase. / Kajitani, Noriko; Kobuchi, Hirotsugu; Fujita, Hirofumi; Yano, Hiromi; Fujiwara, Takuzo; Yasuda, Tatsuji; Utsumi, Kozo.

In: Bioscience, Biotechnology and Biochemistry, Vol. 71, No. 11, 2007, p. 2701-2711.

Research output: Contribution to journalArticle

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AB - 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.

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