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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/L607    most recent 00302.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Merker, M. P. Articles by Krenz, G. S. Search for Related Content PubMed PubMed Citation Articles by Merker, M. P. Articles by Krenz, G. S.

Influence of pulmonary arterial endothelial cells on quinone redox status: effect of hyperoxia-induced NAD(P)H:quinone oxidoreductase 1

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

Submitted 13 July 2005 ; accepted in final form 19 October 2005

The objective of this study was to examine the impact of chronic hyperoxic exposure (95% O₂ for 48 h) on intact bovine pulmonary arterial endothelial cell redox metabolism of 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ). DQ or durohydroquinone (DQH₂) was added to normoxic or hyperoxia-exposed cells in air-saturated medium, and the medium DQ concentrations were measured over 30 min. DQ disappeared from the medium when DQ was added and appeared in the medium when DQH₂ was added, such that after 15 min, a steady-state DQ concentration was approached that was 4.5 times lower for the hyperoxia-exposed than the normoxic cells. The rate of DQ-mediated reduction of the cell membrane-impermeant redox indicator, potassium ferricyanide [Fe(CN)], was also approximately twofold faster for the hyperoxia-exposed cells. Inhibitor studies and mathematical modeling suggested that in both normoxic and hyperoxia-exposed cells, NAD(P)H:quinone oxidoreductase 1 (NQO1) was the dominant DQ reductase and mitochondrial electron transport complex III the dominant DQH₂ oxidase involved and that the difference between the net effects of the cells on DQ redox status could be attributed primarily to a twofold increase in the maximum NQO1-mediated DQ reduction rate in the hyperoxia-exposed cells. Accordingly, NQO1 protein and total activity were higher in hyperoxia-exposed than normoxic cell cytosolic fractions. One outcome for hyperoxia-exposed cells was enhanced protection from cell-mediated DQ redox cycling. This study demonstrates that exposure to chronic hyperoxia increases the capacity of pulmonary arterial endothelial cells to reduce DQ to DQH₂ via a hyperoxia-induced increase in NQO1 protein and total activity.

duroquinone; pulmonary endothelial cells; mathematical modeling

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