INHIBITION OF MITOCHONDRIAL H2S SYNTHESIS INCREASES OXIDATIVE STRESS AND IMPAIRS THE ELECTRON TRANSPORT CHAIN FUNCION
A.Yu. Luchkova, N.A. Strutynska, Yu.P. Korkach, V.F. Sagach
Bogomoletz Institute of Physiology, NAS Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz64.06.009
Abstract
In our research we studied the influence of mitochondrial H2S
synthesis inhibition with o-carboxymethylhydroxylamine (50
mg/kg, in vivo) on oxidative stress indicators and respiratory
chain function. It was found that the amount of hydrogen
sulfide in the mitochondria and blood plasma of experimental
animals was reduced by 25 and 45%, respectively. The rate of
of (.)O2(-) and (.)OH-radicals generation increased both in mitochondria
and plasma, indicating an intensification of free radicals
formation process with a decrease in H2S content, which is a
known antioxidant. In case of inhibition of the H2S enzyme
production, the activity of the constitutive NO synthase in
both mitochondria and blood plasma was decreased by 20 and
24%, respectively. In this case, the activity of inducible NOS
in organelles increased by 3.27 times, indicating a significant increase in the formation of NO, which is likely to participate
in the synthesis of peroxynitrite. The inhibition of the
mitochondrial pathway to hydrogen sulfide synthesis impairs
the functional capacity of the electron transport chain, which
manifested itself in lowering the rate of oxygen consumption
in the states V2, V3 and V4, as well as indicators of RCR and
ADP / O. This, perhaps, is the main reason for the deterioration
of functional functioning of the heart, because the efficiency
of the energy supply of the myocardium, for which the mitochondria
correspond, is crucial for the work of the heart.
Keywords:
heart; mitochondria; respiratory chain; hydrogen sulfide; oxidative stress; active forms of oxygen
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