Carbon monoxide specifically inhibits cytochrome C oxidase of human mitochondrial respiratory chain
Carbon monoxide specifically inhibits cytochrome C oxidase of human mitochondrial respiratory chain
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DOI：
10.1034/j.1600-0773.2003.930306.x
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Miró, O
中科院分区：
文献类型：
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作者：
Alonso, JR;Cardellach, F;Miró, O
一氧化碳（CO）毒性是组织缺氧和细胞水平上直接CO介导的损伤的组合的结果，因为并非所有的体征和症状都可以仅通过碳氧血红蛋白的形成来解释。线粒体，特别是电子传递链，似乎是CO在亚细胞水平的目标。然而，CO在人类线粒体呼吸链的单个复合物中的直接作用尚未完全阐明。我们在这里研究了在体外的影响CO对个人的线粒体呼吸链的线粒体复合物。我们从10名接受髋关节置换手术的健康人身上获得肌肉组织。将分离的线粒体在50、100和500 ppm的CO浓度下孵育5分钟。之后，线粒体呼吸链的单个复合物的酶活性进行了评估，在体外和那些在基础（合成空气无CO）条件下获得的比较。细胞色素c氧化酶（线粒体呼吸链复合物IV）活性从836+/-439 nmol/min下降。空气孵育至670+/-401、483+/-182和379+/-131 nmol/min后的线粒体蛋白mg。/ 50，100和500 ppm的CO孵育后，分别（20%，42%和55%的细胞色素c氧化酶活性下降）mg。细胞色素c氧化酶的这种逐渐降低被发现具有统计学意义（P
Carbon monoxide (CO) toxicity is the result of a combination of tissue hypoxia and direct CO-mediated damage at a cellular level, since not all the signs and symptoms presented can be explained only by the formation of carboxyhaemoglobin. Mitochondria, specially the electron transport chain, seem to be the target for CO at a subcellular level. However, the direct effect of CO in individual complexes of the human mitochondrial respiratory chain has not been completely elucidated. We here studied the in vitro effect of CO on individual complexes of the mitochondrial respiratory chain of human mitochondria. We obtained muscle tissue from 10 healthy people who underwent orthopaedic surgery for hip replacement. Isolated mitochondria were incubated for 5 min. under CO concentrations of 50, 100 and 500 ppm. Afterwards, enzymatic activities of individual complexes of the mitochondrial respiratory chain were assessed in vitro and compared with those obtained in basal (synthetic air without CO) conditions. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) activity showed a decrease from 836+/-439 nmol/min./mg of mitochondrial protein after air incubation to 670+/-401, 483+/-182, and 379+/-131 nmol/min./mg after 50, 100 and 500 ppm of CO incubation, respectively (20%, 42% and 55% decrease in cytochrome c oxidase activity). This gradual decrease in cytochrome c oxidase was found to be statistically significant (P