Coenzyme Q1redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

Abstract

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q1(CoQ1) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O2for 48 h) rats. CoQ1or its hydroquinone (CoQ1H2) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ1H2and CoQ1were measured. CoQ1H2appeared in the venous effluent when CoQ1was infused, and CoQ1appeared when CoQ1H2was infused. In normoxic lungs, CoQ1H2efflux rates when CoQ1was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ1H2oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ1H2efflux rates when CoQ1was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ1reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ1during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ1to CoQ1H2due to a depression in complex I activity.