Qian Liu and Wei-Guo Xu contributed equally to this work.
Cigarette smoke-induced skeletal muscle atrophy is associated with up-regulation of USP-19 via p38 and ERK MAPKs†
Article first published online: 18 AUG 2011
Copyright © 2011 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 112, Issue 9, pages 2307–2316, September 2011
How to Cite
Liu, Q., Xu, W.-G., Luo, Y., Han, F.-F., Yao, X.-H., Yang, T.-Y., Zhang, Y., Pi, W.-F. and Guo, X.-J. (2011), Cigarette smoke-induced skeletal muscle atrophy is associated with up-regulation of USP-19 via p38 and ERK MAPKs. J. Cell. Biochem., 112: 2307–2316. doi: 10.1002/jcb.23151
- Issue published online: 18 AUG 2011
- Article first published online: 18 AUG 2011
- Accepted manuscript online: 18 APR 2011 08:26AM EST
- Manuscript Accepted: 8 APR 2011
- Manuscript Received: 25 SEP 2010
- Shanghai Natural Science Foundation Project. Grant Number: 05ZR14063
- Ubiquitin-specific protease-19;
- Muscle wasting;
- L6 myotubes;
- Cigarette smoke extract;
- MAPK pathway
Ubiquitin-specific proteases (USPs) deubiquitinate ubiquitin–protein conjugates in the ubiquitin–proteasome system. Previous research shows that ubiquitin-specific protease-19 (USP-19) is up-regulated in mammalian skeletal muscle in some degradative conditions, such as including fasting, diabetes, dexamethasone treatment, and cancer, and its function is associated with muscle atrophy. However, it is still unclear whether USP-19 is involved in muscle atrophy induced by chronic obstructive pulmonary disease. Rats exposed to chronic cigarette smoke and L6 myotubes incubated with cigarette smoke extract (CSE) were studied here. Using western blot analysis and quantitative real-time polymerase chain reaction (qPCR), we observed over-expression of USP-19 and down-regulation of myosin heavy chain (MHC) in both models. Moreover, CSE exposure inhibited myogenic differentiation and myotube formation in L6 myotubes. To explore the mechanism underlying these effects, we investigated the levels of phosphorylated mitogen-activated protein kinases (MAPKs) and total MAPKs. Exposing myotubes to CSE resulted in the general activation of MAPKs such as p38, JNK, and ERK1/2. The ERK inhibitor PD98059 and the p38 inhibitor SB203580 significantly blocked the increase in USP-19 gene expression induced by CSE. Our findings suggest that USP-19 is associated with muscle atrophy in response to cigarette smoke and is a potential therapeutic target. CSE promotes myotube wasting in culture partly by inhibiting myogenic differentiation and acts via p38 and ERK MAPK to stimulate expression of USP-19 in vitro. J. Cell. Biochem. 112: 2307–2316, 2011. © 2011 Wiley-Liss, Inc.