MITOCHONDRIAL DYSFUNCTION IN THE AGING HEART IS ACCOMPANIED BY CONSTITUTIVE NO-SYNTHASES UNCOUPLING ON THE BACKGROUND OF OXIDATIVE AND NITROSATIVE STRESS
N.A. Strutynska, А.V. Kotsiuruba, A.Yu. Budko, L.A. Mys, V.F. Sagach
O.O. Bogomoletz Institute of Physiology, National Academy
of Sciences of Ukraine, Kyiv
We investigated the sensitivity of mitochondrial permeability
transition pore (MPTP) opening to its inductor calcium, as well
as indicators of oxidative and nitrosative stress in adult and old
rat heart mitochondria and heart tissues. The coupling index of
constitutive Ca2+/calmodulin-dependent NO-synthase (сNOS)
was calculated based on experimentally found parameters.
The aging is characterized by oxidative and nitrosative stress,
which accompanied by a decrease of the cNOS coupling index
and an increased sensitivity of MPTP to calcium. We found
that in the heart mitochondria of old rats such oxidative stress
indicators as the rate of generation of superoxide (•
OH) anion radicals were significantly increased (in
4 and 2,7 times respectively). Also, increased levels of urea
and products of early lipid peroxidation – conjugated dienes
display the intensification of oxidative stress. Such indicators
of nitrosative stress as nitrate reductase and iNOS activity were
also enhanced. At the same time under aging the NO2
generated when the heart oxygenation is normal, nitrosothiols
pools and the activity of cNOS were decreased. It is due to
the enhanced level of cNOS uncoupling, resulting in increased
oxidative stress. It was also shown the lower level of hydrogen
sulfide (H2S) in old rat heart mitochondria. Thus, we observed
the increased sensitivity of MPTP to calcium, due to decreased
concentration of its inhibitors nitric oxide and hydrogen sulfide
and increased levels of its inducers ROS and RNS in old rat
mitochondria; heart; cNOS uncoupling; oxidative stress; aging rats
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