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Myocardial protection by selective poly(ADP-ribose) polymerase inhibitors
Krisztina Kovacs1, Ambrus Toth, Peter Deres
1Department of Biochemistry and Medical Chemistry, and.
Abstract:
During ischemia-reperfusion, reactive oxygen species are generated along the mitochondrial respiratory chain and induce lipid peroxidation, protein oxidation and DNA damage. Single-strand DNA breaks are the most potent activators of poly(ADP-ribose) polymerase (PARP); prolonged action of PARP culminates in intracellular oxidized nicotinamide adenine dinucleotide (NAD(+)) and ATP depletion. The integrity of cellular components and the myocardial energy metabolism can be preserved by using PARP inhibitors under conditions of ischemia and reperfusion. Oxidative stress is capable of activating the phosphoinositol-3-kinase-Akt/protein kinase B signalling pathway, which is further enhanced if treated with PARP inhibitors. Akt, in turn, promotes the survival of cardiomyocytes by inhibiting apoptotis, and causing metabolic adjustment and vasodilation in the jeopardized myocardium.
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