Influence of Pulmonary Arterial Endothelial Cells on Quinone Redox Status: Effect of Hyperoxia-induced NAD(P)H:quinone oxidoreductase 1

Authors

Marilyn P. Merker, Medical College of Wisconsin
Said H. Audi, Marquette UniversityFollow
Robert D. Bongard, Medical College of Wisconsin
Brian J. Lindemer, Medical College of Wisconsin
Gary S. Krenz, Marquette UniversityFollow

Document Type

Article

Language

eng

Format of Original

13 p.

Publication Date

3-2006

Publisher

American Physiological Society

Source Publication

American Journal of Physiology: Lung Cellular and Molecular Physiology

Source ISSN

1040-0605

Original Item ID

doi: 10.​1152/​ajplung.​00302.​2005

Abstract

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.

Comments

Journal of Physiology: Lung Cellular and Molecular Physiology, Vol. 290, No. 3 (March 2006): L607-L619. DOI.

Recommended Citation

Merker, Marilyn P.; Audi, Said H.; Bongard, Robert D.; Lindemer, Brian J.; and Krenz, Gary S., "Influence of Pulmonary Arterial Endothelial Cells on Quinone Redox Status: Effect of Hyperoxia-induced NAD(P)H:quinone oxidoreductase 1" (2006). Biomedical Engineering Faculty Research and Publications. 9.
https://epublications.marquette.edu/bioengin_fac/9