Inhibition of mitochondrial respiration by nitric oxide is independent of membrane fluidity modulation or oxidation of sulfhydryl groups.
Nitric oxide (NO) modulates the fluidity of a variety of membranes. Thus, the aim of the present work was to study if the inhibitory effect of NO on mitochondrial respiration is associated with its effects on membrane fluidity. Liver mitochondria and an inner mitochondrial membrane fraction (IMMF) were isolated from male Wistar rats by differential centrifugation. Oxygen consumption was measured polarographically and fluidity by the fluorescence polarization method. S-nitroso-N-acetylpenicillamine (SNAP) was used as a NO donor. It was observed that NO decreased IMMF fluidity and oxygen consumption in a concentration dependent fashion. However, SAM a fluidizing agent that prevented the decrement in fluidity produced by SNAP, failed to preserve oxygen consumption. Protection of sulfhydryl groups with dithiotreitol was utilized to evaluate the role of oxidation of these groups on IMMF respiration. Incubation with dithiotreitol did not preserve IMMF oxygen consumption. The data shown herein suggest that NO inhibits the respiratory chain by a mechanism not involving the modulation of membrane fluidity or the oxidation of sulfhydryl groups. Thus, it seems that the mechanism by which NO modulates mitochondrial respiration is by cytochrome oxidase inhibition, because (as reported by others) low concentrations of NO specifically inhibit reversibly cytochrome oxidase in competition with oxygen.
Pérez-Rojas
Jazmin M
JM
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D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D010396:Penicillamine