Ischemia/reperfusion (I/R) injury is an inescapable event during some therapeutic procedures, such as organ transplantation, cardiopulmonary bypass, aortic cross-clamping, etc. Dysfunctional purine metabolism is one of the important mechanisms in I/R injury. A novel deuterated porphyrin peptide Deuterohaemin-AlaHisThrValGluLys (DHP6) possesses both microperoxidase activity and cell-permeability. This peptide can increase the expression of superoxide dismutase 3, a scavenger enzyme in oxidative stress that can catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen. It can catalyze the conversion of hydrogen peroxideto water and protect cultured rat lens crystalline from cataracts induced by galactose. It can also improve cell survival and prevent apoptosis. Our previous study demonstrated that DHP6 protects murine hearts against ischemia-reperfusion injury, but its mechanism remains unclear. In this study, we examined the effect of DHP6 on purine metabolism in the perfused mouse heart subjected to ischemia/reperfusion injury. 14 mouse hearts were isolated and perfused in constant pressure mode of Langendorff system. After 30-minute stabilization period, half of the hearts were treated with 3 μM of DHP6 and the other half were treated with equivalent normal saline for 10 minutes. All the hearts were then subjected to global normothermic no-flow ischemia for 30 minutes followed by the reperfusion for 120 minutes with corresponding treatments. At the end of the procedure, each heart was freeze-clamped under liquid nitrogen for further assays. Lowry protein assay and high performance liquid chromatograph (HPLC) were used to determine metabolites ATP, ADP, AMP, adenosine, inosine, inosine monophosphate, hypoxanthine, xanthine, coenzyme A (CoA), acetyl-CoA and Malonyl-CoA in frozen heart tissues. Our data indicate that DHP6 prevents purine nucleotide degradation and preserves high energy phosphates.

Effect of deuterohemin-AlaHisThrValGluLys on purine metabolism in the perfused mouse heart subjected to ischemia/reperfusion injury

2019 Fall National Meeting

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