Alonso Jose-Ramon, Cardellach Francesc, López Sònia, Casademont Jordi, Miró Oscar
Department of Internal Medicine, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.
Pharmacol Toxicol. 2003 Sep;93(3):142-6. doi: 10.1034/j.1600-0773.2003.930306.x.
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<0.001). Other complex activities showed no any significant variation. Carbon monoxide is toxic for mitochondria in man, altering the mitochondrial respiratory chain at the cytochrome c oxidase level. This inhibition in cytochrome c oxidase may play a role in the development of the symptoms observed in acute CO poisoning, and in some diseases related to smoking.
一氧化碳（CO）中毒是组织缺氧与细胞水平上CO直接介导的损伤共同作用的结果，因为并非所有出现的体征和症状都能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，似乎是亚细胞水平上CO的作用靶点。然而，CO对人类线粒体呼吸链各个复合体的直接作用尚未完全阐明。我们在此研究了CO对人线粒体呼吸链各个复合体的体外作用。我们从10名因髋关节置换接受骨科手术的健康人身上获取肌肉组织。分离出的线粒体在50、100和500 ppm的CO浓度下孵育5分钟。之后，在体外评估线粒体呼吸链各个复合体的酶活性，并与在基础（不含CO的合成空气）条件下获得的活性进行比较。细胞色素c氧化酶（线粒体呼吸链复合体IV）的活性在空气孵育后为836±439 nmol/分钟/毫克线粒体蛋白，在50、100和500 ppm的CO孵育后分别降至670±401、483±182和379±131 nmol/分钟/毫克（细胞色素c氧化酶活性分别降低20%、42%和55%）。发现细胞色素c氧化酶的这种逐渐降低具有统计学意义（P<0.001）。其他复合体的活性未显示出任何显著变化。一氧化碳对人体线粒体有毒，在细胞色素c氧化酶水平上改变线粒体呼吸链。细胞色素c氧化酶的这种抑制作用可能在急性CO中毒以及一些与吸烟相关疾病所观察到的症状发展中起作用。
