4-Hydroxy-3,5,3′,4′-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria

Hirofumi Fujita, Yuya Okimura, Toshihiko Utsumi, Shigeyuki Kitamura, Hiroaki Kuroki, Takemi Otsuki, Junzo Sasaki, Akihiko Kashiwagi, Kozo Utsumi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Although much information about the apoptotic and other detrimental actions of polychlorinated biphenyls (PCBs) has been accumulated, the critical role of mitochondrial damage in such toxic action remains to be clarified. We have previously shown that PCBs affect various functions in isolated mitochondria. Recent studies have revealed that mitochondria play an important role in apoptosis through membrane permeability transition (MPT), and that Ca 2+ induces classic MPT characterized by depolarization and swelling of the mitochondria, thereby releasing cytochrome c in a cyclosporin A-sensitive mechanism [Free Rad. Res. 38, 29-35, 2004]. In the present study we investigated the effect of 4-hydroxy-3,5,3′,4′-tetrachlorobiphenyl (4-OH-TCB) on isolated rat liver mitochondria in order to help clarify the effect of PCBs on MPT. Biochemical analysis revealed that 4-OH-TCB induced calcium release, reactive oxygen species (ROS) generation, depolarization, swelling and cytochrome c release in isolated rat liver mitochondria in a time and concentration dependent manner. These 4-OH-TCB-induced changes in mitochondrial function were found to be inhibited by the presence of cyclosporin A, suggesting an classic type of MPT. It is concluded that 4-OH-TCB induces MPT together with ROS generation, causing apoptosis in certain cells.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
Journaljournal of clinical biochemistry and nutrition
Volume38
Issue number3
DOIs
Publication statusPublished - May 2006

Keywords

  • Apoptosis
  • Membrane permeability transition
  • Mitochondria
  • Polychlorinated biphenyls
  • Reactive oxygen species

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry

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