Cigarette Smoke–induced Oxidative Stress A Role in Chronic Obstructive Pulmonary Disease Skeletal Muscle Dysfunction American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 477-488, (2010) ENIGMA in COPD Project
Rationale: Inflammation and oxidative stress contribute to muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). Oxidants contained in cigarette smoke (CS) induce adverse effects on tissues through oxidative phenomena.
Objectives: To explore oxidative stress and inflammation in quadriceps of human smokers and in diaphragm and limb muscles of guinea pigs chronically exposed to CS.
Methods: Muscle function, protein oxidation and nitration, antioxidants, oxidized proteins, inflammation, creatine kinase activity, and lung and muscle structures were investigated in vastus lateralis of smokers, patients with COPD, and healthy control subjects and in diaphragm and gastrocnemius of CS-exposed guinea pigs at 3, 4, and 6 months.
Measurements and Main Results: Compared with control subjects, quadriceps muscle force was mildly but significantly reduced in smokers; protein oxidation levels were increased in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed animals; glycolytic enzymes, creatine kinase, carbonic anydrase-3, and contractile proteins were significantly more carbonylated in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed guinea pigs. Chronic CS exposure induced no significant rise in muscle inflammation in either smokers or rodents. Muscle creatine kinase activity was reduced only in patients with COPD and in both diaphragm and gastrocnemius of CS-exposed animals. Guinea pigs developed bronchiolar abnormalities at 4 months of exposure and thereafter.
Conclusions: CS exerts direct oxidative modifications on muscle proteins, without inducing any significant rise in muscle inflammation. The oxidative damage to muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle loss and dysfunction in smokers and patients with COPD.
AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Oxidative stress is a proposed contributor to chronic obstructive pulmonary disease (COPD) muscle dysfunction. Oxidants contained in cigarette smoke induce adverse effects on tissues through oxidative modifications of key biological structures. It remains to be elucidated whether chronic cigarette smoking induces direct oxidative damage in skeletal muscles.
What This Study Adds to the Field Chronic cigarette smoking exerts direct oxidative modifications on muscle proteins, without inducing significant rise in either molecular or cellular muscle inflammation. Importantly, the oxidative damage to specific muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle mass loss and dysfunction in smokers and patients with COPD.