10 august 2010 - Press release
This study is published in the American Journal of Respiratory and Critical Care Medicine, the most prestigious journal in the respiratory field
Cigarette smoke causes molecular alterations in muscles which contribute to developing muscle dysfunction, a symptom which is very common in COPD (Chronic Obstructive Pulmonary Disease) patients. This is the first study in which proteins involved in metabolism and muscle contraction are shown to have higher levels of oxidation as a result of tobacco smoke, which could cause alterations in the structure and function of muscle fibres.
The study was directed by Esther Barreiro, coordinator of the IMIM (Hospital del Mar Research Institute) research group on molecular mechanisms of lung cancer predisposition, and includes the collaboration of the Hospital Clínic of Barcelona and the Hospital de Cruces of Bilbao.
The researchers assessed the effects of being chronically exposed to cigarette smoke on two large interrelated molecular mechanisms: oxidative stress, or an imbalance between the production of oxidants and antioxidants in cells, and inflammation. Researchers studied, on the one hand, its effects on the quadriceps muscle of smokers not suffering from heart or lung diseases, and on the other hand, its effects on the limb muscles (gastrocnemius) and the diaphragm, the most important respiratory muscle, of animals exposed to cigarette smoke for 3, 4 and 6 months. Similarly, the same molecular mechanisms were analysed in COPD patients, a disease which is closely related to the chronic effects of cigarette smoke.
According to Esther Barreiro, head of the study, the results show that: “both in smokers and in the guinea pigs chronically exposed to cigarette smoke, tobacco smoke directly causes oxidative alterations in muscle proteins without a significant rise in inflammation", which means that of these two molecular mechanisms, oxidative stress is the most important, and inflammation bears no relevance. This oxidative damage of muscle proteins precedes the pulmonary alterations observed in the animal model and could be involved in the development of muscle dysfunction in COPD patients. “Tobacco smoke per se causes this toxicity in muscle cells even in the absence of any bronchial alterations and independently of the subject’s possible pulmonary alterations”, explains Esther Barreiro.
Previous studies carried out by the same researchers on tumour cachexia animal models had highlighted the involvement of oxidative stress in inducing structural alterations in muscle fibres. Researchers had observed a reduction in the size of type II fibres, which are in charge of quick muscle movements in the limbs, such as the gastrocnemius muscle, as well as the possibility that this oxidative stress could increase the susceptibility of proteins to be degraded by protein destruction or cell proteolytic systems (2010). Likewise, other studies published by this same team of researchers have highlighted the damaging effects of the excess of oxidants on muscle dysfunction in COPD patients subjected to intense physical exercise (2009).
According to the researchers, the conclusions stemming from this study are that muscle dysfunction and underlying molecular alterations described in COPD patients can occur before the onset of lung disease, and not as a result of it. The muscle alterations caused by cigarette smoke components would worsen COPD patients’ ability to exert themselves and their quality of life. Future studies will enable us to identify the specific molecular mechanisms by which muscle protein oxidation alters the function of these in smokers.
Reference Article: Cigarette smoke-induced oxidative stress: a role in COPD skeletal muscle dysfunction. Esther Barreiro, Víctor I. Peinado, Juan B. Galdiz, Elisabet Ferrer, Judith Marin-Corral, Francisco Sánchez, Joaquim Gea, Joan Albert Barberà, on behalf of the ENIGMA in COPD project. American Journal of Respiratory and Critical Care Medicine