Department of Internal Medicine, College of Medicine, Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Am J Respir Crit Care Med. 2010 Apr 15;181(8):797-805. doi: 10.1164/rccm.200906-0936OC. Epub 2010 Jan 28.
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.
(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.
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.
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.
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.
烟酰胺 N-甲基转移酶（NNMT）在慢性阻塞性肺疾病（COPD）患者的股四头肌中高度表达。然而，其在这些患者膈肌中的表达尚未被评估。NNMT 在 COPD 患者骨骼肌中诱导的功能意义也尚不清楚。
（1）比较 COPD 患者膈肌和股四头肌中的 NNMT 表达。（2）确定促炎细胞因子对 NNMT 表达的影响。（3）评估 NNMT 对肌生成（卫星细胞迁移和增殖）和氧化应激防御指数的影响。
从 13 例中重度 COPD 患者和 8 例对照者中获得肋膈肌活检。从 12 例 COPD 患者和 14 例对照者中获得股四头肌活检。
COPD 患者的膈肌和股四头肌中的 NNMT 表达显著升高；然而，与膈肌（2 倍）相比，股四头肌中 NNMT 表达的相对诱导更高（10 倍）。NNMT 表达与 COPD 的严重程度和肢体肌肉消耗呈负相关。在骨骼肌成肌细胞中，NNMT 表达被 IL-6、转化生长因子β和肿瘤坏死因子-α显著诱导。NNMT 在成肌细胞中的过表达可引发显著的增殖和迁移增加，但对细胞死亡无影响。当 NNMT 过表达时，暴露于 H2O2 下的成肌细胞中羰基的形成明显减弱。
COPD 患者骨骼肌中 NNMT 表达的上调可能代表一种适应性反应，旨在改善肌生成并抵抗氧化应激。
