RT Journal Article
ID 7a1b0f0049c55a61
A1 Strutynska, Nataliya A. 
A1 Kotsuruba, Anatoliy V. 
A1 Budko, Alina Yu. 
A1 Mys, Lidiya A. 
A1 Sagach, Vadim F. 
T1 Age-Associated Mitochondrial Dysfunction in the Heart Accompanied by Constitutive NO-Synthases Uncoupling on the Background of Oxidative and Nitrosative Stress
JF International Journal of Physiology and Pathophysiology
JO IJPP
YR 2017
FD 2017-08-24
VO 8
IS 2
SP 141
OP 150
K1 mitochondria
K1 heart
K1 cNOS uncoupling
K1 oxidative stress
K1 aging
K1 rats
AB We investigated the sensitivity of mitochondrial permeability transition pore (MPTP) opening to its inductor calcium and indicators of oxidative and nitrosative stress in the heart mitochondria and heart tissues of adult and old rats. The coupling index of constitutive Ca<sup>2&#43;</sup>/calmodulin-dependent NO-synthase (cNOS) was calculated based on experimentally found parameters. It has been revealed that aging, which is characterized by oxidative and nitrosative stress, is accompanied by a decrease of cNOS coupling index and an increase of MPTP sensitivity to calcium. We also found increased levels of oxidative stress in the heart mitochondria of old rats. In particular, the rate of superoxide (&#183;O<sub>2</sub><sup>&minus;</sup>) and hydroxyl (&#183;OH) generation
increased by 4 and 2.7 times, respectively, the levels of urea and products of early lipid peroxidation (diene conjugates) increased by ten times, indicating the intensification of oxidative stress. Simultaneously, we observed enhanced nitrosative stress, as evidenced by an increase of nitrate reductase and iNOS activities. At the same time, the pools of NO<sub>2</sub><sup>&minus;</sup> and lowmolecular weight nitrosothiols, usually generated when the heart oxygenation is normal, as well as Ca<sup>2&#43;</sup>/calmodulin-dependent cNOS activity were reduced. The latter was due to enhanced cNOS uncoupling, which resulted in oxidative stress enhancement. In addition, hydrogen sulphide (H<sub>2</sub>S) level decreased significantly in the heart mitochondria of old rats. Against the background of those processes, we observed an increased MPTP sensitivity to calcium, induced by a decrease in the concentration of nitric oxide and hydrogen sulphide as the inhibitory agents for MPTP, and an increase in the levels of ROS and RNS as inducers of its opening in the heart mitochondria of old rats.

PB Begell House
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