ACONITASE IS A SENSITIVE AND CRITICAL TARGET OF OXYGEN POISONING IN CULTURED-MAMMALIAN-CELLS AND IN RAT LUNGS
ACONITASE IS A SENSITIVE AND CRITICAL TARGET OF OXYGEN POISONING IN CULTURED-MAMMALIAN-CELLS AND IN RAT LUNGS
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DOI：
10.1073/pnas.91.25.12248
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发表时间：
1994-12-06
影响因子：
11.1
通讯作者：
WHITE, CW
中科院分区：
文献类型：
--
作者：
GARDNER, PR;NGUYEN, DDH;WHITE, CW
在培养的人上皮样A549细胞和大鼠肺中测定高氧对超氧化物敏感的柠檬酸循环酶乌头酸酶活性的影响。在暴露于600 mmHg（1 mmHg = 133 Pa）的PO2 24小时期间，观察到A549细胞中>80%的顺乌头酸酶活性的快速和进行性损失。线粒体呼吸能力的抑制与A549细胞暴露于高氧中乌头酸酶活性的丧失相关，并且这种效应可以被乌头酸酶的代谢毒物氟乙酸盐（或氟柠檬酸盐）模仿。大鼠暴露于760毫米汞柱或635毫米汞柱的大气PO2 24小时分别造成73%和61%的总肺顺乌头酸酶活性下降。我们建议，早期失活的乌头酸酶和柠檬酸循环的能量产生和生物合成反应的抑制，导致暴露于高氧期间观察到的肺损伤和水肿的后遗症。
The effect of hyperoxia on activity of the superoxide-sensitive citric acid cycle enzyme aconitase was measured in cultured human epithelial-like A549 cells and in rat lungs. Rapid and progressive loss of >80% of the aconitase activity in A549 cells was seen during a 24-hr exposure to a PO2 of 600 mmHg (1 mmHg = 133 Pa). Inhibition of mitochondrial respiratory capacity correlated with loss of aconitase activity in A549 cells exposed to hyperoxia, and this effect could be mimicked by fluoroacetate (or fluorocitrate), a metabolic poison of aconitase. Exposure of rats to an atmospheric PO2 of 760 mmHg or 635 mmHg for 24 hr caused respective 73% and 61% decreases in total lung aconitase activity. We propose that early inactivation of aconitase and inhibition of the energy-producing and biosynthetic reactions of the citric acid cycle contribute to the sequelae of lung damage and edema seen during exposure to hyperoxia.