Dynamic movement of cytochrome c from mitochondria into cytosol and peripheral circulation in massive hepatic cell injury

Background: In the process of apoptosis, it is known that the transition of cytochrome c from mitochondria into the cytosol occurs, and tumor necrosis factor (TNF)-alpha is one of the molecules responsible for this event. But in the state of hypercytokine induced by D-galactosamine (D-GaIN)/Lipopolysaccharide (LPS), the localization of cytochrorne c is little known. Methods: Rats were administrated with D-GaIN(700 mg/kg)/LPS(200 mug/kg). Blood and tissue samples were collected and examined for levels of pro-inflammatory cytokines, the apoptosis of liver cells, and the localization of cytochrome c. Result: Before administration of D-GaIN/LPS, cytochrome c was definitely localized in the mitochondria. At 2 h after simultaneous administration of D-GaIN/LPS, cytochrome c had accumulated in the cytosol following abrupt increases of plasma TNF-alpha. Massive cell destruction due to apoptosis proved by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was observed in liver tissue 4 It later and markedly increased levels of cytochrome c were detected in the plasma 12 h after D-GaIN/LPS administration. Conclusion: Liver injury induced by simultaneous administration of D-GaIN/LPS was closely associated with the production of TNF-alpha, and also with the dynamic movement of cytochrome c from the mitochondria into the cytosol, and then into the systemic circulation. The detection of plasma cytochrorne c levels may be a useful clinical tool for the detection of apoptosis in vivo.