Evidence from a recent study indicates that glucocorticoids (GCs) mediate skeletal muscle proteolysis during sepsis via the GC receptor (GR) pathway. Attempts to identify the mechanisms regulating GR gene expression in skeletal muscle during sepsis have been hampered by the lack of an appropriate in vitro model system that can mimic in vivo septic conditions. In the present study, we report that GR gene transcription in L6 myocytes in vitro is up-regulated by treatment with sera from septic rats in a manner similar to that measured in septic rats in vivo. Sera from septic rats were collected from animals in which sepsis was induced by caecal ligation and puncture and from control rats that were sham-operated. Finally, by treating L6 myotubes with the GR antagonist RU 38486, thereby preventing sepsis-induced GR transcription, we confirmed that the possible septic effect on the GR was due to increased GCs. L6 myocytes treated with sera from septic rats might therefore be useful as an experimental model for identifying the molecular mechanisms by which the GR regulates muscle cachexia during sepsis. Furthermore, RU 38486 inhibited the sepsis-induced increase in total and myofibrillar energy-dependent protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated rats, as measured by release of tyrosine and 3-methylhistidine respectively. Our results demonstrate for the first time that sepsis induces GR transcription in skeletal muscle, and supports the hypothesis that the GC-induced proteolysis under sepsis is partially a consequence of GR activation.
Skip Nav Destination
Article navigation
September 2003
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
September 01 2003
Sepsis induces the transcription of the glucocorticoid receptor in skeletal muscle cells
Xiaoyan SUN;
*Department of Surgery, The University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, U.S.A.
†Shriners Hospitals for Children, 3229 Burnet Avenue, Cincinnati, OH 45229, U.S.A.
Correspondence: Dr X. Sun (e-mail [email protected]).
Search for other works by this author on:
Joshua M. V. MAMMEN;
Joshua M. V. MAMMEN
*Department of Surgery, The University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, U.S.A.
Search for other works by this author on:
Xintian TIAN
Xintian TIAN
‡Department of Molecular and Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 10 2003
Revision Received:
June 03 2003
Accepted:
June 10 2003
Accepted Manuscript online:
June 10 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 105 (3): 383–391.
Article history
Received:
March 10 2003
Revision Received:
June 03 2003
Accepted:
June 10 2003
Accepted Manuscript online:
June 10 2003
Connected Content
A retraction has been published:
Sepsis induces the transcription of the glucocorticoid receptor in skeletal muscle cells
Citation
Xiaoyan SUN, Joshua M. V. MAMMEN, Xintian TIAN; Sepsis induces the transcription of the glucocorticoid receptor in skeletal muscle cells. Clin Sci (Lond) 1 September 2003; 105 (3): 383–391. doi: https://doi.org/10.1042/CS20030087
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |