Corticosteroids and muscle wasting: role of transcription factors, nuclear cofactors, and hyperacetylation.
OBJECTIVE
The purpose of this review is to discuss novel insight into mechanisms of glucocorticoid-regulated muscle wasting, in particular the role of transcription factors and nuclear cofactors. In addition, novel strategies that may become useful in the treatment or prevention of glucocorticoid-induced muscle wasting are reviewed.


RESULTS
Studies suggest that glucocorticoid-induced upregulation of the transcription factors Forkhead box O 1 and CCAAT/enhancer-binding protein beta and downregulation of MyoD and myogenin are involved in glucocorticoid-induced muscle wasting. In addition, glucocorticoid-induced hyperacetylation caused by increased expression of the nuclear cofactor p300 and its histone acetyl transferase activity and decreased expression and activity of histone deacetylases plays an important role in glucocorticoid-induced muscle proteolysis and wasting. Other mechanisms may also be involved in glucocorticoid-induced muscle wasting, including insulin resistance and store-operated calcium entry. Novel potential strategies to prevent or treat glucocorticoid-induced muscle wasting include the use of small molecule histone deacetylase activators, dissociated glucocorticoid receptor agonists, and 11beta-hydroxysteroid dehydrogenase type 1 inhibitors.


CONCLUSIONS
An increased understanding of molecular mechanisms regulating glucocorticoid-induced muscle wasting will help develop new strategies to prevent and treat this debilitating condition.
Hasselgren
Per-Olof
PO
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. phasselg@bidmc.harvard.ed
Alamdari
Nima
N
Aversa
Zaira
Z
Gonnella
Patricia
P
Smith
Ira J
IJ
Tizio
Steven
S
D000107:Acetylation; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000009:adverse effects*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009133:Muscular Atrophy / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D017570:MyoD Protein; D018008:Myogenin; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; D006655:Histone Deacetylases
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