Nitric oxide inhibits mitochondrial monoamine oxidase activity and decreases outer mitochondria membrane fluidity.
The recent finding that mitochondria contain a nitric oxide (NO) synthase suggests that this compound is involved in the regulation of various mitochondrial functions. Monoamine oxidase (MAO) is embedded in the outer mitochondrial membrane. NO modulates membrane fluidity. Thus, the aim of the present work was to study the effect of NO on mitochondrial MAO activity and membrane fluidity. An outer mitochondrial membrane fraction (OMMF) was obtained from rat liver. OMMF was incubated with various concentrations of S-nitroso-N-acetylpenicillamine (SNAP), a NO donor. MAO activity and fluidity were measured by a spectrophotometric assay and by the polarization of fluorescence technique, respectively. It was found that small concentrations of SNAP (0.4-40 microM) were capable of inhibiting MAO activity but unable to decrease fluidity significantly. In contrast, larger amounts of SNAP (40-300 microM) effectively decreased membrane fluidity, but were not able to further decrease MAO activity. This information suggests that mitochondrial MAO and membrane fluidity possess different sensitivity to the effect of NO. Unfortunately, the mechanism by which NO inhibits MAO remains unknown at present. However, it seems likely that the effect of NO on MAO activity is by a direct interaction of the compound or a metabolite to the protein.
Muriel
Pablo
P
Sección Externa de Farmacología, CINVESTAV-IPN, Apdo. Postal 14-740, México, D.F. 07000, Mexico. pamuriel@mail.cinvest.mx
Pérez-Rojas
Jazmin M
JM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D008996:Monoamine Oxidase Inhibitors; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D008995:Monoamine Oxidase; D010396:Penicillamine