Effect of burn injury on glucocorticoid receptor binding activity in rat muscle.
Burn injury is associated with increased muscle proteolysis and up-regulated gene expression in the proteolytic pathway. Glucocorticoids (GCs) are the most important mediator of burn injury induced muscle cachexia. However, the understanding of the mechanisms of GCs action in response to burn injury remains elusive. It is well known that GC acts by binding its own receptor. Therefore, in the present study, we examined the influence of burn injury on the hormone binding activity of the glucocorticoid receptor (GR) in skeletal muscle. Burn injury resulted in increased hormone binding activity in extensor digitorum longus (EDL) and soleus muscles. Scatchard plots revealed that the increased GR hormone binding activity reflected increased numbers of hormone binding sites, whereas receptor affinity for GCs was unchanged. Western blot analysis showed that dissociation of GR/heat shock protein 90 heterocomplex or increase in GR protein may account for the effect of burn injury. The GR antagonist RU 38486 blocked the burn injury-induced increase in GR hormone binding activity, implicating a positive regulatory effect of GCs on GR binding activity under the present experimental conditions.
Sun
Xiaoyan
X
Department of Surgery, University of Cincinnati, Cincinnati, Ohio, and Shriners Hospitals for Children, Cincinnati, OH 45267-0558, USA. sunxn@email.uc.edu
Fischer
David R
DR
Yang
Mingyan
M
Tian
Tony X
TX
D000818:Animals; D001665:Binding Sites; D002056:Burns / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D005938:Glucocorticoids / Q000378:metabolism; D006614:Hindlimb; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012867:Skin / Q000293:injuries*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D006728:Hormones; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone