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1 Department of Biomedical Engineering, Marquette University, Milwaukee, WI, USA; Department of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
2 Department of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
3 Department of Mathematics Statistics and Computer Science, Marquette University, Milwaukee, WI, USA
4 Department of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Research Service, Zablocki VA Medical Center, Milwaukee, WI, USA
5 Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pharmacology/Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA; Research Service, Zablocki VA Medical Center, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: audis{at}mu.edu.
NAD(P)H:quinone oxidoreductase (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to sub-lethal hyperoxia (85% O2) for seven or more days stimulates adaptation to the otherwise lethal effects of > 95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia (85% O2 for 48 hours or 21 days) affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured the appearance of DQH2 in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats that had been exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution, and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2, and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21 day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, from 1.95 ± 0.14 (SE) to 4.04 ±0.21 µmol/min, and the apparent Michaelis-Menten constant for DQ reduction, Kma, from 44 ± 11 to 149 ±11 µM. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NOQ1 activity in 21-day hyperoxic lungs (~34%). The increase in Kma could be accounted for by ~ 40 % increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.
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  S. H. Audi, M. P. Merker, G. S. Krenz, T. Ahuja, D. L. Roerig, and R. D. Bongard Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia J Appl Physiol, October 1, 2008; 105(4): 1114 - 1126. [Abstract] [Full Text] [PDF]
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M. P. Merker, S. H. Audi, R. D. Bongard, B. J. Lindemer, and G. S. Krenz Influence of pulmonary arterial endothelial cells on quinone redox status: effect of hyperoxia-induced NAD(P)H:quinone oxidoreductase 1 Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L607 - L619. [Abstract] [Full Text] [PDF]
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