Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs
Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs
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DOI：
10.1152/ajplung.00064.2005
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发表时间：
2005-11-01
影响因子：
4.9
通讯作者：
Merker, MP
中科院分区：
文献类型：
--
作者：
Audi, SH;Bongard, RD;Merker, MP
NAD（P）H：醌氧化还原酶1（NQO 1）在醌化合物2，3，5，6-四甲基-1，4-苯醌（杜醌，DQ）通过大鼠肺还原为杜氢醌（DQH（2））中起主导作用。将成年大鼠暴露于85%的O-2中>= 7天，可刺激其适应> 95% O-2的其他致死效应。本研究的目的是研究是否暴露于高氧影响肺NQO 1活性的成年大鼠DQ减少通过肺的速度来衡量。我们测量了暴露于室内空气或85%O-2的大鼠的离体灌注肺的肺动脉中不同浓度DQ输注期间静脉流出物中DQH（2）的出现。我们还评估了高氧对血管通过时间分布的影响，并测定了肺匀浆中NQO 1活性和蛋白质。结果表明，暴露于85%O-2 21天可增加肺将DQ还原为DQH的能力（2），NQO 1是常氧和高氧肺中主要的DQ还原酶。动力学分析显示，21天的高氧暴露增加了肺DQ减少的最大速率，V-max，和DQ减少的表观Michaelis-Menten常数，K-ma。Vmax的增加表明高氧诱导的肺细胞NQO 1活性增加，可从血管区域获得DQ，与21天高氧肺中肺匀浆NQO 1活性增加定性一致，但不定量。在21天的高氧肺血管通过时间异质性增加40%，可以解释Kma的增加。
NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone ( duroquinone, DQ) to durohydroquinone (DQH(2)) on passage through the rat lung. Exposure of adult rats to 85% O-2 for >= 7 days stimulates adaptation to the otherwise lethal effects of > 95% O-2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH(2) appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O-2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O-2 for 21 days increases lung capacity to reduce DQ to DQH(2) and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, V-max, and the apparent Michaelis-Menten constant for DQ reduction, K-ma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by similar to 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.