Journal of Applied Physiology AJP: Advances in Physiology Education
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J Appl Physiol 105: 1114-1126, 2008. First published August 14, 2008; doi:10.1152/japplphysiol.00177.2008
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Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

Said H. Audi,1,3 Marilyn P. Merker,4,5,6 Gary S. Krenz,2 Taniya Ahuja,1 David L. Roerig,4,5,6 and Robert D. Bongard3

Departments of 1Biomedical Engineering, 2Mathematics, Statistics and Computer Science, Marquette University; Departments of 3Pulmonary and Critical Care Medicine, 4Anesthesiology, and 5Pharmacology/Toxicology, Medical College of Wisconsin; and 6Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin

Submitted 14 February 2008 ; accepted in final form 14 August 2008

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% O2 for 48 h) rats. CoQ1 or its hydroquinone (CoQ1H2) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ1H2 and CoQ1 were measured. CoQ1H2 appeared in the venous effluent when CoQ1 was infused, and CoQ1 appeared when CoQ1H2 was infused. In normoxic lungs, CoQ1H2 efflux rates when CoQ1 was 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 CoQ1H2 oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ1H2 efflux rates when CoQ1 was 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 CoQ1 reduction, 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 CoQ1 during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ1 to CoQ1H2 due to a depression in complex I activity.

mathematical modeling; NADH: ubiquinone oxidoreductase; NAD(P)H: quinone oxidoreductase 1; ubiquinol-cytochrome-c oxidoreductase


Address for reprint requests and other correspondence: S. H. Audi, Research Service 151, Zablocki VAMC, 5000 W. National Ave., Milwaukee, WI 53295 (e-mail: audis{at}mu.edu)






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