Pyruvate metabolism of perfused rat lungs after exposure to 100% oxygen.
Pyruvate metabolism of perfused rat lungs after exposure to 100% oxygen.
复制标题
丙酮酸%20代谢%20of%20灌注%20rat%20肺%20after%20暴露%20至%20100%%20氧气。
DOI：
10.1152/jappl.1986.60.5.1605
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Bowen-Kelly,E
中科院分区：
文献类型：
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作者：
Bassett,DJ;Bowen-Kelly,E
先前对肺匀浆的研究表明，肺氧毒性部分是由于线粒体能量代谢受到抑制。在这项研究中，通过测量[1-14C]-丙酮酸在灌注肺中产生的14CO2来确定线粒体代谢，在暴露于100% O2 0、3、6、12和24小时后分离。在2,4-二硝基苯酚（DNP）解偶联氧化磷酸化的正常和刺激条件下进行了测量。用5% CO2在O2中通气，用12.5 mM 14C标记的丙酮酸灌注100分钟。未暴露的肺产生14CO2的线性速率为121 +/- 16 mumol/h/g dry wt (n = 5)，灌注0.8 mMDNP时最大刺激率为84%。暴露于100% O2中24小时对14CO2的产生没有显著影响。相比之下，DNP在暴露于100% O2超过3小时的肺中不能显著刺激丙酮酸对CO2的代谢。这些数据表明，O2暴露使肺线粒体无法响应与DNP解偶联相关的ATP需求增加。因此，能量代谢受损是氧中毒的一个重要早期事件。
Previous studies with lung homogenates have suggested that pulmonary O2 toxicity is in part a result of inhibited mitochondrial energy metabolism. In this study, mitochondrial metabolism was determined by measurements of 14CO2 production from [1–14C]-pyruvate in perfused lungs, isolated after 0, 3, 6, 12, and 24 h of exposure to 100% O2. Measurements were made under normal and stimulated conditions brought about by uncoupling oxidative phosphorylation with 2,4-dinitrophenol (DNP). Lungs were ventilated with 5% CO2 in O2 and perfused for 100 min with 12.5 mM 14C labeled pyruvate. Unexposed lungs gave a linear rate of 14CO2 production of 121 +/- 16 mumol/h/g dry wt (n = 5), which was maximally stimulated 84% by perfusion with 0.8 mMDNP. Twenty-four hours of exposure to 100% O2 did not significantly affect 14CO2 production. In contrast, DNP failed to significantly stimulate pyruvate metabolism to CO2 in lungs exposed for greater than 3 h to 100% O2. These latter data suggested that O2 exposure makes lung mitochondria unable to respond to increased ATP demands associated with DNP uncoupling. Compromised energy metabolism is therefore an important early event in O2 toxicity.