Effect of smoking cessation on mitochondrial respiratory chain function

Effect of smoking cessation on mitochondrial respiratory chain function
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DOI:
10.1081/clt-120021102
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发表时间:
2003-01-01
期刊:
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子:
--
通讯作者:
Miró, O
Miró, O
中科院分区:
其他
文献类型:
--
作者:
Cardellach, F;Alonso, JR;Miró, O

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Objective.尽管复合物IV活性的抑制是最一致和最相关的发现,但慢性吸烟与淋巴细胞中多种线粒体呼吸链(MRC)功能障碍相关。这些线粒体异常被认为是与烟草消费相关的疾病的发病机制。我们评估了重度吸烟者戒烟后外周血淋巴细胞MRC功能。患者和方法。我们研究了10名健康的慢性吸烟者(年龄43 +/- 6岁; 50%为女性)在戒烟前(to)、戒烟后7天(t(1))和28 - 42天的外周血淋巴细胞MRC功能。通过测量呼出气中的碳氧血红蛋白水平和一氧化碳(CO)浓度来确定戒烟情况。10名年龄和性别匹配的健康非吸烟者被用作对照。用Ficoll梯度分离淋巴细胞,用Bradford技术测定蛋白质含量。MRC功能通过两种方法进行研究:1)通过分光光度法分析复合物II、III和IV的单个酶活性; 2)在淋巴细胞透化后,使用丙酮酸、琥珀酸和甘油-3-磷酸(分别为复合物I、II和III底物)通过极谱法测量氧消耗。酶和氧化活性通过柠檬酸合酶活性校正。结果与对照组相比,吸烟者表现出复合物IV活性(p = 0.05)和完整淋巴细胞呼吸(p = 0.05)的显著降低。8名长期吸烟者在研究期间保持戒烟。戒烟与复合物IV(p = 0.01)和复合物III(p = 0.05)活性的显著恢复相关。氧化活性在研究期间未显示任何变化。结论慢性吸烟与MRC的复合物IV和III活性的降低有关,其在停止吸烟后恢复到正常值。
Objective. Chronic smoking has been associated with diverse mitochondrial respiratory chain (MRC) dysfunction in lymphocytes, although inhibition of complex IV activity is the most consistent and relevant finding. These mitochondrial abnormalities have been proposed to contribute to pathogenesis of diseases associated with tobacco consumption. We assessed MRC function in peripheral lymphocytes from heavy smokers after cessation in smoking habit. Patients and Methods. We studied MRC function from peripheral lymphocytes of 10 healthy chronic smoker individuals (age 43 +/- 6 years; 50% women) before cessation of tobacco consumption (to), and 7 (t(1)) and 28 42) days after cessation. Smoking abstinence was ascertained by measuring carboxyhemoglobin levels and carbon monoxide (CO) concentration in exhaled breath. Ten healthy nonsmoker individuals matched by age and gender were used as controls. Lymphocytes were isolated by Ficoll's gradient, and protein content was determined by Bradford's technique. MRC function was studied through double means: 1) individual enzyme activities of complex II, III, and IV were analyzed by means of spectrophotometry; 2) oxygen consumption was measured polarographically using pyruvate, succinate, and glycerol-3-phosphate (complex I, II, and III substrates, respectively) after lymphocyte permeabilization. Enzyme and oxidative activities were corrected by citrate synthase activity. Results. Smokers showed a significant decrease in complex IV activity (p = 0.05) and also in respiration of intact lymphocytes (p = 0.05) compared to controls. Eight chronic smokers remained abstinent during the study. Smoking cessation was associated with a significant recovery of complex IV (p = 0.01) and complex III (p = 0.05) activities, Oxidative activities did not show any change during the study. Conclusion. Chronic smoking is associated with a decrease of complex IV and III activities of MRC, which return to normal values after cessation of tobacco smoking.