Mitochondrial permeability transition and cytochrome c release in ischemia-reperfusion injury of the rat liver

Akihiko Hirakawa, Naoshi Takeyama, Toshio Nakatani, Takaya Tanaka

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Background. We investigated whether ischemia-reperfusion causes activation of caspases and whether this activation is related to cytochrome c release from the mitochondria into the cytosol as a result of the mitochondrial inner membrane permeability transition. Materials and methods. Rats were subjected to 30 min to 120 min of hepatic ischemia followed by 6 h of reperfusion. Cyclosporin A or ruthenium red (inhibitors of the mitochondrial inner membrane permeability transition) was given intravenously at 60 and 30 min before ischemia, respectively. Results. Reperfusion after ischemia caused the release of liver enzymes accompanied by mitochondrial membrane depolarization, DNA fragmentation, and translocation of cytochrome c from the mitochondria into the cytosol. Accumulation of cytochrome c in the cytosol and activation of caspase-3-like protease was already detected during ischemia and before reperfusion. Pretreatment with cyclosporin A or ruthenium red significantly ameliorated the loss of the mitochondrial membrane potential, the increase of plasma membrane permeability, the cytosolic accumulation of cytochrome c, DNA fragmentation, and caspase-3-like protease activation. Conclusions. The mitochondrial inner membrane permeability transition occurs during ischemia and/or after reperfusion, resulting in translocation of cytochrome c and activation of caspases.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalJournal of Surgical Research
Volume111
Issue number2
DOIs
Publication statusPublished - 15-05-2003

All Science Journal Classification (ASJC) codes

  • Surgery

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