[Nitric oxide suppresses permeability transition pore opening and enhances calcium uptake in mitochondria in vivo].
The influence of an NO donor, nitroglycerine (NG) on Ca2+ accumulation in rat heart and liver mitochondria was studied. A rapid dose-dependent increase in Ca(2+)-uptake was observed within 5 min after NG injection in vivo, with a peak in NG concentration of 0.5-1.0 mg/kg body weight. There is a correlation between a dose-dependent increase in Ca(2+)-accumulating capacity of mitochondria and sharp dose-dependent rise in stable NO metabolites level (NO2-, NO3- and nitrosothiols) and reactive oxygen species (H2O2 and hydroxyl radical, *OH) as well as lipid oxidation products (diene conjugates), the markers of the oxidative damage of the organelles in mitochondria in comparison to a whole tissue (liver) where only moderate increase of ROS and NO metabolites was detected. A 20-30-fold increase of NO3- level from 32. +/- 2.6 to 736.4 +/- 96.5 nmol/mg protein (p < 0.05) and from 45.4 +/- 6.2 to 1395.0 +/- 121.1 nmol/mg protein (p < 0.05) in liver and heart mitochondria respectively also provide a strong evidence for nitrosative stress. The results obtained suggest that calcium elimination from cytosol and its increased accumulation in mitochondria (likely dependent on permeability transition pore blockade by NO) could account for the cardioprotective action of NG although resulted in the development of oxidative stress with following long-term alterations of the energy supply and metabolism of subcellular structures.
Akopova
O V
OV
Kotsiuruba
A V
AV
Tkachenko
Iu P
IuP
Sahach
V F
VF
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D002118:Calcium