戒烟对线粒体呼吸链功能的影响。

Effect of smoking cessation on mitochondrial respiratory chain function.

作者信息

Cardellach Francesc, Alonso Josep R, López Sònia, Casademont Jordi, Miró Oscar

机构信息

Mitochondrial Research Laboratory, Muscle Research Unit, Department of Internal Medicine, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.

出版信息

J Toxicol Clin Toxicol. 2003;41(3):223-8. doi: 10.1081/clt-120021102.

DOI:10.1081/clt-120021102

PMID:12807302

Abstract

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 (t0), and 7 (t1) and 28 (t2) 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.

摘要

目的

慢性吸烟与淋巴细胞中多种线粒体呼吸链（MRC）功能障碍有关，尽管对复合体IV活性的抑制是最一致且相关的发现。这些线粒体异常被认为与烟草消费相关疾病的发病机制有关。我们评估了重度吸烟者戒烟后外周淋巴细胞中的MRC功能。

患者与方法

我们研究了10名健康慢性吸烟者（年龄43±6岁；50%为女性）在停止烟草消费前（t0）以及停止后7天（t1）和28天（t2）外周淋巴细胞的MRC功能。通过测量羧基血红蛋白水平和呼出气体中的一氧化碳（CO）浓度来确定戒烟情况。选取10名年龄和性别相匹配的健康非吸烟者作为对照。通过Ficoll梯度分离淋巴细胞，并用Bradford技术测定蛋白质含量。通过两种方式研究MRC功能：1）通过分光光度法分析复合体II、III和IV的个体酶活性；2）在淋巴细胞透化后，使用丙酮酸、琥珀酸和3-磷酸甘油（分别为复合体I、II和III的底物）通过极谱法测量氧气消耗。酶活性和氧化活性通过柠檬酸合酶活性进行校正。