Role of mitochondrial electron transport complex I in coenzyme Q1 reduction by intact pulmonary arterial endothelial cells and the effect of hyperoxia.

Abstract

The objective was to determine the impact of intact normoxic and hyperoxia-exposed (95% O(2) for 48 h) bovine pulmonary arterial endothelial cells in culture on the redox status of the coenzyme Q(10) homolog coenzyme Q(1) (CoQ(1)). When CoQ(1) (50 microM) was incubated with the cells for 30 min, its concentration in the medium decreased over time, reaching a lower level for normoxic than hyperoxia-exposed cells. The decreases in CoQ(1) concentration were associated with generation of CoQ(1) hydroquinone (CoQ(1)H(2)), wherein 3.4 times more CoQ(1)H(2) was produced in the normoxic than hyperoxia-exposed cell medium (8.2 +/- 0.3 and 2.4 +/- 0.4 microM, means +/- SE, respectively) after 30 min. The maximum CoQ(1) reduction rate for the hyperoxia-exposed cells, measured using the cell membrane-impermeant redox indicator potassium ferricyanide, was about one-half that of normoxic cells (11.4 and 24.1 nmol x min(-1) x mg(-1) cell protein, respectively). The mitochondrial electron transport complex I inhibitor rotenone decreased the CoQ(1) reduction rate by 85% in the normoxic cells and 44% in the hyperoxia-exposed cells. There was little or no inhibitory effect of NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors on CoQ(1) reduction. Intact cell oxygen consumption rates and complex I activities in mitochondria-enriched fractions were also lower for hyperoxia-exposed than normoxic cells. The implication is that intact pulmonary endothelial cells influence the redox status of CoQ(1) via complex I-mediated reduction to CoQ(1)H(2), which appears in the extracellular medium, and that the hyperoxic exposure decreases the overall CoQ(1) reduction capacity via a depression in complex I activity.

• Authors: Marilyn P Merker, Said H Audi, Brian J Lindemer, Gary S Krenz, Robert D Bongard
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 293 Issue 3 Pg. L809-19 (Sep 2007) ISSN: 1040-0605 [Print] United States
• PMID: 17601793 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Benzoquinones
• Culture Media
• Enzyme Inhibitors
• Ferricyanides
• Ubiquinone
• hexacyanoferrate III
• Tolonium Chloride
• L-Lactate Dehydrogenase
• Electron Transport Complex I
• Ubiquinone Q1
• duroquinone

Topics

• Aerobiosis (drug effects)
• Animals
• Benzoquinones (pharmacology)
• Cattle
• Cell Survival (drug effects)
• Cells, Cultured
• Chromatography, High Pressure Liquid
• Culture Media
• Electron Transport Complex I (antagonists & inhibitors, metabolism)
• Endothelial Cells (drug effects, enzymology)
• Enzyme Inhibitors (pharmacology)
• Ferricyanides (pharmacology)
• Hyperoxia (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Mitochondria (drug effects, enzymology, metabolism)
• Oxidation-Reduction (drug effects)
• Oxygen Consumption (drug effects)
• Pulmonary Artery (cytology, drug effects, enzymology)
• Spectrophotometry
• Tolonium Chloride (pharmacology)
• Ubiquinone (analysis, metabolism, pharmacology)