Specificity of coenzyme Q inhibition of an aging-related cell surface NADH oxidase (ECTO-NOX) that generates superoxide.
Our laboratories have described a novel class of ectoproteins at the cell surface with both NADH or hydroquinone oxidase (NOX) and protein disulfide-thiol interchange activities (ECTO-NOX proteins). The two activities exhibited by these proteins alternate to generate characteristic patterns of oscillations where the period length is independent of temperature. The period length for the constitutive ECTO-NOX is 24 min. Here we describe a distinctive age-related ECTO-NOX (arNOX) whose activity is blocked by coenzyme Q10. arNOX occurs exclusively in aged cells and tissues. The period length of the oscillations is 26 min. Rather than reducing 1/2 O2 to H2O, electrons are transferred to O2 to form superoxide. Superoxide formation was demonstrated by superoxide dismutase-sensitive reduction of ferricytochrome c and by reduction of a superoxide-specific tetrazolium salt. Quinone inhibition was given by coenzymes Q8, 9 and Q10 but not by Q0, Q2, Q4, Q6 or 7. The arNOX provides a mechanism to propagate reactive oxygen species generated at the cell surface to surrounding cells and circulating lipoproteins of importance to atherogenesis. Inhibition of arNOX by dietary coenzyme Q10 provides a rational basis for dietary coenzyme 10 use to retard aging-related arterial lesions.
Morré
Dorothy M
DM
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907, USA. morred@cfcs.purdue.edu
Morré
D James
DJ
D000375:Aging; D045304:Cytochromes c / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009243:NAD / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014451:Ubiquinone / Q000737:chemistry / Q000494:pharmacology*
D004220:Disulfides; D004791:Enzyme Inhibitors; D011506:Proteins; D013438:Sulfhydryl Compounds; D009243:NAD; D013481:Superoxides; D014451:Ubiquinone; D045304:Cytochromes c; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase