Chorna S. Role of mitochondrial pore in the correction of functional disorders of the heart with aging under conditions of activation of ubiquinone biosynthesis and long-term exercise training.

Dissertation is devoted to the study of changes in the sensitivity of mitochondrial permeability transition pore (MPTP) opening to it inductors and correction of functional disorders of the rat heart with aging under conditions of activation of ubiquinone biosynthesis and long-term exercise training. The results of our research demonstrated that activation of biosynthesis ubiquinone (coenzyme Q (CoQ)) under administration of CoQ biosynthesis precursors - 4-hydroxybenzoic acid, methionine and modulator of CoQ biosynthesis, namely vitamin E increased of CoQ and vitamin E content in old rats heart mitochondria. The activation of ubiqinone biosynthesis and long-term exercise training contributed to cardioprotective effect due to reduced the degree of the ischemia-reperfusion injury in adult and old rat heart, namely the restoration of myocardial contractile function and coronary flow as well as decrease the end diastolic pressure and oxygen cost of the heart compared with control group of the animals during ischemia-reperfusion. Further, under activation of ubiqinone biosynthesis and long-term exercise training it was observed decrease in the sensitivity of MPTP opening to Са2+ and phenilarsin oxide. It was shown that the expression level of mitochondrial uncoupling protein 3 (UCP3) decreased in old rats compared to adult animals. Under activation of endogenous synthesis of CoQ it was observed almost complete restoration of UCP3 expression in old rat heart. Тhe expression level of UCP3 was reduced in heart mitochondria after long-term exercise training rat compared with the control. Besides, it was shown that the components of MPTP voltage-dependent anion channel (VDAC) mRNA expression increased by 1,7 (p<0,05) and mRNA adenine nucleotide translocase (ANT) - in 1,8 (p<0,05) times in the old rats heart in comparison with adult animals. With the method of Western Blott analysis has been shown that the level of VDAC protein expression in the old rat heart also significantly increased compared with adult animals.