Superoxide release from contracting skeletal muscle in pulmonary TNF-α overexpression mice

Li Zuo*, Allison H. Hallman, William J. Roberts, Peter D. Wagner, Michael C. Hogan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Chronic obstructive pulmonary disease (COPD) often results in increased levels of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, which circulates in the blood. However, it is not clear whether pulmonary TNF-α overexpression (a COPD mimic) induces excessive reactive oxygen species (ROS) formation in skeletal muscle and thereby may contribute to the muscle impairment often seen in COPD. We hypothesized that ROS generation in contracting skeletal muscle is elevated when there is TNF-α overproduction in the lung and that this can induce muscle dysfunction. Cytochrome c (cyt c) in the perfusate was used to assay superoxide (O2·-) release from isolated contracting soleus muscles from transgenic mice of pulmonary TNF-α overexpression (Tg+) and wild-type (WT) mice. Our results showed that Tg+muscle released significantly higher levels of O2·- than WT during a period of intense contractile activity (in nmol/mg wt; 17.5 ± 2.3 vs. 4.4 ± 1.3, respectively; n = 5; P < 0.05). In addition, the soleus muscle demonstrated a significantly reduced fatigue resistance in Tg+ mice compared with WT mice. Perfusion of the contracting soleus muscle with superoxide dismutase, which specifically scavenges O2·- in the perfusate, resulted in significantly less cytc reduction, thereby indicating that the type of ROS released from the Tg+muscles is O2·-. Our results demonstrate that pulmonary TNF-α overexpression leads to a greater O2•- release from contracting soleus muscle in Tg+ compared with WT and that the excessive formation of O2·- in the contracting muscle of Tg+ mice leads to earlier fatigue.

Original languageEnglish
Pages (from-to)R75-R81
Number of pages7
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1
Publication statusPublished - 1 Jan 2014
Externally publishedYes


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