Tetramethylphenylenediamine protects the isolated heart against ischaemia-induced apoptosis and reperfusion-induced necrosis.

摘要: BACKGROUND AND PURPOSE Cytochrome c when released from mitochondria into cytosol triggers assembly of the apoptosome resulting in caspase activation. Recent evidence suggests that reduced cytochrome is unable to activate cascade. In this study, we investigated whether a chemical reductant c, N,N,N′,N′-tetramethylphenylene-1,4-diamine (TMPD), which have previously shown block c-induced activation, could prevent ischaemia-induced apoptosis rat perfused heart. EXPERIMENTAL APPROACH The Langendorff-perfused hearts were pretreated with TMPD and subjected stop-flow ischaemia or ischaemia/reperfusion. activation caspases (measured as DEVD-p-nitroanilide-cleaving activity), nuclear cardiomyocytes by dUTP nick end labelling assay), mitochondrial cytosolic levels spectrophotometrically elisa), reperfusion-induced necrosis activity creatine kinase perfusate) assessed. KEY RESULTS We found perfusion strongly inhibited ischaemia- ischaemia/reperfusion-induced partially prevented cardiomyocytes. did not release cytosol. also necrosis. CONCLUSIONS IMPLICATIONS These results suggest related molecules might be used protect heart against damage induced mechanism protective effect probably involves electron reduction (without decreasing its release) then inhibits caspases.