Faculty Collaboration Database

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 2006 Mar;290(3):L607-19

Date

10/26/2005

Pubmed ID

16243901

DOI

10.1152/ajplung.00302.2005

Scopus ID

2-s2.0-33644947752 (requires institutional sign-in at Scopus site)   15 Citations

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 approximately 15 min, a steady-state DQ concentration was approached that was approximately 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)6(3-)], 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.

Author List

Merker MP, Audi SH, Bongard RD, Lindemer BJ, Krenz GS

Author

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Benzoquinones
Cattle
Cytosol
Endothelium, Vascular
Ferricyanides
Genes, Dominant
Humans
Hydroquinones
Hyperoxia
NAD(P)H Dehydrogenase (Quinone)
Oxidation-Reduction
Oxygen Consumption
Pulmonary Artery
Pulmonary Circulation