Abstract
We tested the hypotheses that low concentration of H2O2 attenuates the Ca2+ paradox (Ca2+ PD) injury, and that activation of protein kinase C (PKC) and/or ATP-sensitive potassium channel (KATP) are involved in the protective effects of H2O2. Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 min of Ca2+ depletion followed by 10 min of Ca2+ repletion). Functional and biochemical effects of H2O2 and other interventions on the cell injury induced by the Ca2+ PD were assessed. In the Ca2+ PD hearts pretreated with 20 mumol/l H2O2, left ventricular end-diastolic pressure and coronary flow were significantly preserved. Furthermore, peak lactate dehydrogenase release was significantly decreased and ATP contents were more preserved, compared with non-treated Ca2+ PD hearts. H2O2-treated hearts also showed remarkable preservation of cell structure. Addition of a specific PKC inhibitor, chelerythrine during H2O2 treatment completely abolished the beneficial effects of H2O2 on the Ca2+ PD. Similarly, an activator of PKC. Phorbol 12-myristate 13 acetate mimicked the protection by H2O2. Furthermore, pretreatment with a KATP opener, cromakalim also provided protection similar to H2O2 against the Ca2+ PD injury. However, a specific KATP inhibitor, glibenclamide was not able to completely block the effects of H2O2. These findings suggest that pretreatment with low concentration of H2O2 provides significant protection against the lethal injury of Ca2+ PD in rat hearts. PKC-mediated signaling pathways appear to play a crucial role in the protection against the Ca2+ PD injury.
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