Duroquinone reduction during passage through the pulmonary circulation
Duroquinone reduction during passage through the pulmonary circulation
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DOI：
10.1152/ajplung.00185.2003
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发表时间：
2003-11-01
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
肺可以显著影响氧化还原活性血浆成分的氧化还原状态。我们的目的是检查方面的动力学和机制，确定肺处置的氧化还原活性化合物通过肺循环。以2，3，5，6-四甲基-1，4-苯醌[杜醌（DQ）]作为模型两亲性醌还原酶底物在大鼠和小鼠肺上进行实验。我们测量了在肺静脉流出液中注射或同时输注DQ或DQH 2到肺动脉流入液中的DQ和durohydroquinone（DQH（2））浓度。在大鼠和小鼠肺中DQ还原为DQH 2的最大净速率相似，分别为4.9和2.5 μ mol。min（-1）。g肺干重（-1）。净速率显然是DQ和DQH 2自由渗透进入氧化还原反应组织部位的结果，主要是双香豆素敏感的DQ还原为DQH（2）和氰化物敏感的DQH（2）再氧化回DQ。双香豆素敏感性沿着大鼠肺组织中NAD（P）H-醌氧化还原酶1（NQO 1）的免疫可检测表达，表明细胞质NQO 1是DQ减少的主要部位。氰化物对DQH 2氧化的影响表明，氧化的主要位点是线粒体电子传递链的复合物III。如果一个设想DQ作为模型化合物，用于检查两亲性NQO 1基板在肺中的处置，结果是一致的肺NQO 1在确定这种化合物在循环中的氧化还原状态的作用。对于DQ，作用是将氧化还原循环、氧活化醌转化为稳定的氢醌。
The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redoxactive compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [ duroquinone (DQ)] as a model amphipathic quinone reductase substrate. We measured DQ and durohydroquinone (DQH(2)) concentrations in the lung venous effluent after injecting, or while infusing, DQ or DQH2 into the pulmonary arterial inflow. The maximum net rates of DQ reduction to DQH2 in the rat and mouse lungs were similar to 4.9 and 2.5 mumol . min(-1) . g dry lung wt(-1), respectively. The net rate was apparently the result of freely permeating access of DQ and DQH2 to tissue sites of redox reactions, dominated by dicumarol-sensitive DQ reduction to DQH(2) and cyanide-sensitive DQH(2) reoxidation back to DQ. The dicumarol sensitivity along with immunodetectable expression of NAD(P)H-quinone oxidoreductase 1 (NQO1) in the rat lung tissue suggest cytoplasmic NQO1 as the dominant site of DQ reduction. The effect of cyanide on DQH2 oxidation suggests that the dominant site of oxidation is complex III of the mitochondrial electron transport chain. If one envisions DQ as a model compound for examining the disposition of amphipathic NQO1 substrates in the lungs, the results are consistent with a role for lung NQO1 in determining the redox status of such compounds in the circulation. For DQ, the effect is conversion of a redox-cycling, oxygen-activating quinone into a stable hydroquinone.