Expression and functional significance of nicotinamide N-methyl transferase in skeletal muscles of patients with chronic obstructive pulmonary disease.
BACKGROUND
Nicotinamide N-methyl transferase (NNMT) is highly expressed in quadriceps muscles of patients with chronic obstructive pulmonary disease (COPD). However, its expression in the diaphragm of these patients has not been assessed. The functional significance of NNMT induction in skeletal muscles of patients with COPD is also unknown.


OBJECTIVE
(1) To compare NNMT expressions in the diaphragm and quadriceps muscles of patients with COPD. (2) To identify the influence of proinflammatory cytokines on NNMT expression. (3) To assess the influence of NNMT on indices of myogenesis (satellite cell migration and proliferation) and the defense against oxidative stress.


METHODS
Costal diaphragm muscle biopsies were acquired from 13 patients with moderate and severe COPD and 8 control subjects. Quadriceps muscle biopsies were obtained from 12 patients with COPD and 14 control subjects.


RESULTS
NNMT expressions were significantly elevated in the diaphragm and quadriceps muscles of patients with COPD; however, the relative induction of NNMT expression was greater in the quadriceps muscle (10-fold) than it was in the diaphragm (2-fold). NNMT expressions correlated negatively with the severity of COPD and limb muscle wasting. In skeletal myoblasts, NNMT expression was significantly induced by IL-6, transforming growth factor beta, and tumor necrosis factor-alpha. Overexpression of NNMT in myoblasts triggered a significant increase in proliferation and migration, but had no influence on cell death. Carbonyl formation, induced by exposing myoblasts to H(2)O(2), was significantly attenuated when NNMT was overexpressed.


CONCLUSIONS
Up-regulation of NNMT expression in the skeletal muscles of patients with COPD may represent an adaptive response designed to improve myogenesis and defend against oxidative stress.
Kim
Ho Cheol
HC
Department of Internal Medicine, College of Medicine, Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Mofarrahi
Mahroo
M
Vassilakopoulos
Theodoros
T
Maltais
Francois
F
Sigala
Ioanna
I
Debigare
Richard
R
Bellenis
Ioannis
I
Hussain
Sabah N A
SN
D000368:Aged; D000818:Animals; D001706:Biopsy; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003964:Diaphragm / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000201:enzymology*; D050903:Nicotinamide N-Methyltransferase / Q000378:metabolism*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D052097:Quadriceps Muscle / Q000201:enzymology; D012720:Severity of Illness Index
D016207:Cytokines; D050903:Nicotinamide N-Methyltransferase