ACTIVATION OF ENDOGENOUS HYDROGEN SULFIDE SYNTHESIS INHIBITS MITOCHONDRIAL PERMEABILITY TRANSITION PORE OPENING AND RESTORES CONSTITUTIVE NO-SYNTHASE COUPLING IN OLD RAT HEART
L.A. Mys, N.A. Strutynska, V.R. Strutynskyi, V.F. Sagach
O.O. Bogomoletz Institute of Physiology National Academy
of Science of Ukraine, Kyiv
cofactor pyridoxal-5-phosphate on the sensitivity of mitochondrial
permeability transition pore (MPTP) opening to
Ca2+ as natural inducer in old rat heart, as well as the H2S
content and oxidative and nitrosative stress indicators in heart
mitochondria. It was shown that in old rats oxidative and nitrosative
stress developed which accompanied by a decrease
of the constitutive Ca2+-dependent NO-synthase (cNOS)
coupling index. P5P application inhibited Ca2+-induced MPTP
opening by reducing the sensitivity to the inductor in old rat
heart. H2S synthesis modulator application led to increase
hydrogen sulfide values in 4,2 times and promoted to reduce
the .O2- generation speed in 3,5 times in comparison with
these indicators in old animals. An important consequence of
stimulating of hydrogen sulfide endogenous synthesis in aging
was the increase activity of cNOS in 1,9 times and decrease the
activity of Ca2+-independent inducible NO-synthase (iNOS)
in 4,3 times in heart mitochondria. Under these conditions
in organelles cNOS coupling index increased in 8,7 times
relative values in old animals. Thus, H2S acts as a regulator
of MPTP opening and content NO, increasing activity cNOS
and recoverability of enzyme coupled state, indicating the
importance of this gaseous transmitter in the pathology of the
hydrogen sulfide; cNOS coupling; oxidative and nitrosative stress; aging; mitochondria; heart; rats.
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