Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis.
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 treatment with glucocorticoids (GCs). 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 after cecal ligation and puncture and from sham-operated control rats. Sepsis resulted in a two- to threefold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased 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.
Sun
Xiaoyan
X
Department of Surgery, University of Cincinnati, 231 Albert Sabin Way, Mail Location 0558, Cincinnati, Ohio 45267-0558, USA. sunxn@email.uc.edu
Wray
Curtis
C
Tian
Xintian
X
Hasselgren
Per-Olof
PO
Lu
James
J
D000818:Animals; D002100:Cachexia / Q000378:metabolism / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D000071247:Uncoupling Protein 3; D015854:Up-Regulation
D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D003907:Dexamethasone