Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease.
Skeletal muscle dysfunction contributes to poor exercise performance in patients with chronic obstructive pulmonary disease (COPD). Increased oxygen radicals and nitric oxide (NO) have been proposed as mechanisms. In this study, we assessed the levels of protein oxidation (carbonyl formation), lipid peroxidation (4-hydroxy-2-nonenal formation), catalase and Mn-superoxide dismutase (Mn-SOD) expressions, nitric oxide synthases (NOSs), and protein tyrosine nitration in quadriceps muscles of 12 patients with patients with COPD and 6 control subjects. Lipid peroxidation was elevated in muscles of patients with patients with COPD as compared with control subjects, but protein oxidation was not. Muscle Mn-SOD but not catalase protein expression was significantly higher (200%) in patients with patients with COPDas compared with control subjects. Expression of neuronal NOS and endothelial NOS isoforms did not differ between control subjects and patients with COPD, whereas no inducible NOS protein expression was detected in limb muscles of the two groups of subjects. In patients with COPD, neuronal NOS expression correlated negatively with the degree of the airway obstruction (%FEV1 predicted). 3-Nitrotyrosine levels were significantly elevated in muscles of patients with COPDas compared with control subjects, and correlated positively with nNOS protein levels. These results indicate the development of both oxidative and nitrosative stresses in the quadriceps of patients with COPD, suggesting their involvement in muscle dysfunction.
Barreiro
Esther
E
Room L3.05, 687 Pine Ave. West, Montreal, PQ, H3A 1A1 Canada.
Gea
Joaquim
J
Corominas
Josep M
JM
Hussain
Sabah N A
SN
D000368:Aged; D002374:Catalase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D007527:Isoenzymes; D002374:Catalase; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase