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

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.

• Authors: Akihiko Hirakawa, Naoshi Takeyama, Toshio Nakatani, Takaya Tanaka
• Journal: The Journal of surgical research (J Surg Res) Vol. 111 Issue 2 Pg. 240-7 (May 15 2003) ISSN: 0022-4804 [Print] United States
• PMID: 12850469 (Publication Type: Journal Article)

Chemical References

• Cytochrome c Group
• Ruthenium Red
• Cyclosporine
• Casp3 protein, rat
• Caspase 3
• Caspases

Topics

• Animals
• Caspase 3
• Caspases (metabolism)
• Cell Membrane Permeability (drug effects)
• Cyclosporine (pharmacology)
• Cytochrome c Group (metabolism)
• Cytosol (metabolism)
• DNA Fragmentation
• Enzyme Activation
• Intracellular Membranes (physiology)
• Liver (blood supply, enzymology, ultrastructure)
• Male
• Membrane Potentials (drug effects)
• Mitochondria, Liver (metabolism, ultrastructure)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism)
• Ruthenium Red (pharmacology)