Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver.

Abstract

Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.

• Authors: J Soeda, S Miyagawa, K Sano, J Masumoto, S Taniguchi, S Kawasaki
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 281 Issue 4 Pg. G1115-23 (Oct 2001) ISSN: 0193-1857 [Print] United States
• PMID: 11557532 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• BH3 Interacting Domain Death Agonist Protein
• Bid protein, rat
• Carrier Proteins
• Caspase Inhibitors
• Cytochrome c Group
• Enzyme Inhibitors
• Proteins
• Tumor Necrosis Factor-alpha
• caspase-activated DNase inhibitor
• Electron Transport Complex IV
• Caspases

Topics

• Animals
• Apoptosis
• Apoptosis Regulatory Proteins
• BH3 Interacting Domain Death Agonist Protein
• Carrier Proteins (metabolism)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Fractionation
• Cytochrome c Group (metabolism)
• Cytoplasm (chemistry)
• Electron Transport Complex IV (metabolism)
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Immunoblotting
• Immunohistochemistry
• In Situ Nick-End Labeling
• Liver (metabolism, pathology)
• Male
• Mitochondria (chemistry, enzymology)
• Proteins (pharmacology)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology)
• Tumor Necrosis Factor-alpha (metabolism)