title: Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen.
abstract: Rat exposure to 60% O(2) (hyper-60) or 85% O(2) (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O(2). The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH(2)), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH(2) and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (V(max1)) and complex III-mediated DQH(2) oxidation (V(max2)) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, V(max1) increased by ∼80%, with no effect on V(max2). Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O(2) observed in hyper-85 rats.
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, WI, USA.
authors.forename: Zhuohui
authors.initials: Z
authors.lastname: Gan
authors.forename: David L
authors.initials: DL
authors.lastname: Roerig
authors.forename: Anne V
authors.initials: AV
authors.lastname: Clough
authors.forename: Said H
authors.initials: SH
authors.lastname: Audi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D018496:Hyperoxia / Q000201:enzymology*; D007201:Indicator Dilution Techniques; D008168:Lung / Q000098:blood supply / Q000201:enzymology*; D008297:Male; D008954:Models, Biological; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III