Submitted on October 16, 2002
Accepted on April 27, 2003
THE EXPRESSION OF UNCOUPLING PROTEIN 3 IS UPREGULATED IN SKELETAL MUSCLE DURING SEPSIS
Xiaoyan Sun1*, Curtis j Wray2, Xintian Tian3, Per-Olof Hasselgren4, and James Lu2
1 Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA; Shriners Hospitals for Children, Cincinnati, Ohio, USA
2 Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
3 Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA
4 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
* To whom correspondence should be addressed. E-mail: sunxn{at}email.uc.edu.
Uncoupling protein 3 (UCP3) is a member of the mitochondrial transporter superfamily that is expressed primarily in skeletal muscle. UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and glucocorticoids (GCs) treatment. The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known. We examined UCP3 gene and protein expression in skeletal muscles from rats following cecal ligation and puncture, and control rats that were sham-operated. Sepsis resulted in a 2 to 3-fold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor (GR) antagonist RU 38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased by 2.4 to 3.6-fold when incubated muscles from normal rats were treated with dexamethasone (DEX) and/or free fatty acids (FFA) ex vivo. In addition, UCP3 mRNA and protein levels were significantly increased in normal rat muscles in vivo with treatment of either DEX or FFA. The results suggest that sepsis upregulates the gene and protein expression of UCP3 in skeletal muscle, which may at least in part be mediated by GCs and FFA.
