| First Author | Zuo L | Year | 2011 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 301 |
| Issue | 4 | Pages | R1025-31 |
| PubMed ID | 21697519 | Mgi Jnum | J:178654 |
| Mgi Id | MGI:5299407 | Doi | 10.1152/ajpregu.00126.2011 |
| Citation | Zuo L, et al. (2011) Effect of pulmonary TNF-alpha overexpression on mouse isolated skeletal muscle function. Am J Physiol Regul Integr Comp Physiol 301(4):R1025-31 |
| abstractText | TNF-alpha is a proinflammatory cytokine that is involved in numerous pathological processes including chronic obstructive pulmonary disease (COPD). In the present study, we used a transgenic mouse model that overexpresses TNF-alpha in the lung (Tg(+)) to test the hypothesis that chronic exposure to TNF-alpha (as seen in COPD) reduces skeletal muscle force production and fatigue resistance, particularly under low Po(2) conditions. At 7-12 mo, body and muscle weight of both extensor digitorum longus (EDL) and soleus were significantly smaller in Tg(+) compared with littermate wild-type (WT) mice; however, the body-to-muscle weight ratio was not different between groups. EDL and soleus muscles were subjected to in vitro fatiguing contractile periods under high ( approximately 550 Torr) and low Po(2) ( approximately 40 Torr). Although all muscles were less fatigue-resistant during low Po(2) compared with high Po(2), only the soleus fatigued more rapidly in Tg(+) mice ( approximately 12%) compared with WT at high Po(2). The maximal tension of EDL was equally reduced in Tg(+) mice (28-34% decrease from WT under both Po(2) conditions); but for soleus this parameter was smaller only under low Po(2) in Tg(+) mice ( approximately 31% decrease from WT). The peak rate of relaxation and the peak rate of contraction were both significantly reduced in Tg(+) EDL muscles compared with WT EDL under low Po(2) conditions, but not in soleus. These results demonstrate that TNF-alpha upregulation in the lung impairs peripheral skeletal muscle function but affects fast- and slow-twitch muscles differentially at high and low Po(2). |
