Aging-Related Cell Surface ECTO-NOX Protein,arNOX,a Preventive Target to Reduce Atherogenic Risk in the Elderly

A family of constitutive cell surface ECTO-NOX proteins capable of oxidizing reduced quinones, initially described as NADH oxidases, has offered an opportunity to formulate, for the first time, a complete electron transport chain from the cytosol to oxygen at the cell surface with the ECTO-NOX proteins acting as the terminal oxidases. The ECTO-NOX proteins of the cell surface have been postulated as well to link the accumulation of lesions in mitochondrial DNA to cell surface accumulations of reactive oxygen species as one consequence of their role as a terminal oxidase in a plasma membrane electron transport chain. Of the several ECTO-NOX proteins now known, one is a novel cell surface form (arNOX) associated with lymphocytes, sera, saliva and perspiration of patients of age 50 or older and is capable of directly reducing ferric cytochrome c through the generation of superoxide. Because of their cell surface location, ECTO-NOX proteins capable of superoxide generation in response to aging would serve to propagate the aging cascade both to adjacent cells and to oxidize circulating lipoproteins. The generation of superoxide associated with aging is inhibited by coenzyme Q₁₀. As such, the findings provide a rational basis for the antiaging activity of circulating coenzyme Q₁₀ in the prevention of atherosclerosis and other aging-related oxidative changes in cell membranes and circulating lipoproteins.