Extracellular reduction of ubiquinone-1 and -10 by human Hep G2 and blood cells.

Ubiquinol-10 (CoQ10H2) is present in human low density lipoproteins (LDL) where it contributes significantly to the antioxidant defenses against radical-mediated oxidative damage. As CoQ10H2 becomes oxidized to ubiquinone-10 (CoQ10) during the earliest stages of in vitro oxidation of LDL, we investigated a possible cellular recycling of oxidized CoQ10H2, adding CoQ10 or its ambiphilic, short-chain analogue ubiquinone-1 (CoQ1), to cells that are exposed to LDL in vivo. Whole blood, isolated red blood cells and human hepatoma Hep G2 cells (used as a model of hepatocytes) rapidly and efficiently reduced added CoQ1 to ubiquinol-1 (CoQ1H2) detectable outside the cells. In whole blood the same steady-state level of CoQ1H2 was reached whether an equimolar amount of CoQ1 or CoQ1H2 was added. Red cell membranes also showed some reducing activity, whereas CoQ1 added to human blood plasma remained largely in its oxidized form. Cell- and membrane-mediated reduction of CoQ1 was enhanced by NADH, FAD, or human plasma. In comparison to this rapid reduction of extracellular CoQ1, formation of CoQ10H2 from CoQ10 incorporated into human LDL by red blood and Hep G2 cells was slow. Our results show that although human blood cells and Hep G2 cells are endowed with a highly reducing activity for CoQ1, the natural CoQ10 does not appear to represent an efficient substrate for this activity.