The Role Of Mitochondrial Permeability Transition In Apoptosis Of Hepatocytes During Ischemia-Reperfusion In Rat Liver

BackgroudHepatic ischemia-reperfusion can lead to cell apoptosis which is associated with injury of liver. The participation of mitochondria in the mechanism of apoptosis has received much attention in recent years. In fact, mitochondria is the most important organelle which plays a key role in apoptosis by releasing cytochrome c. Cytochrome c is well known as a carrier of electrons during respiration. Current evidence indicates that cytochrome c also functions as a major component of apoptosomes to induce apoptosis. Translocation of cytochrome c from mitochondria to the cytoplasm is a key step in the initiation of apoptosis. Cytosolic cytochrome c, released from the mitochondrial intermembrane space to the cytosol, triggers the activation of the caspase family cascade, leading to cell apoptosis. Present studies demonstrated that the release of cytochrome c mainly depends on mitochondrial permeability transition(MPT). This involves the opening of mitochondrial permeability transition pore(PTP), a non-specific pore in mitochondrial membrane, believed to be formed by three-core components namely, the voltage-dependent anion channel(VDAC) of the outer mitochondrial membrane, the adenine nucleotide translocase(ANT) of the inner mitochondrial membrane and cyclophilin-D from the mitochondrial matrix. The PTP opening is coupled with mitochondrial swelling and permeabilization that ultimately leads to the release of cytochrome c and other mitochondrial proteins. Overload of calcium, oxidative stress, and ATP depletion during I/R could induce PTP opening, while it could be inhibited pharmacologically with the immuno-suppressant, cyclosporin A (CsA). CsA has been widely used as an inhibitor of PTP in researches correlated with apoptosis and MPT, especially for example, the protection against I/R injury in brain or heart. But little is known about the role of MPT in apoptosis during hepatic I/R.