Role of glucocorticoids in the molecular regulation of muscle wasting
Autor: | Patrick O'Neal, Per-Olof Hasselgren, Moin U. Fareed, Michael J. Menconi, Vitaliy Poylin, Wei Wei |
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Rok vydání: | 2007 |
Předmět: |
medicine.medical_specialty
Proteasome Endopeptidase Complex Muscle Proteins Biology Critical Care and Intensive Care Medicine Leucine Internal medicine Intensive care medicine Animals Humans Insulin Insulin-Like Growth Factor I Muscle Skeletal Transcription factor Wasting Glucocorticoids Ubiquitins Wasting Syndrome Skeletal muscle Nuclear Proteins Forkhead Transcription Factors Muscle atrophy Endocrinology medicine.anatomical_structure Proteasome CCAAT-Enhancer-Binding Proteins medicine.symptom Signal transduction Glucocorticoid medicine.drug |
Zdroj: | Critical care medicine. 35 |
ISSN: | 0090-3493 |
Popis: | Objective: To review glucocorticoid-regulated molecular mechanisms of muscle wasting. Design: Review of recent literature describing the role of glucocorticoids in the regulation of proteolytic mechanisms, transcription factors, and nuclear cofactors in skeletal muscle during various catabolic conditions. Main Results: Catabolic doses of glucocorticoids induce muscle atrophy both in vivo and in vitro by stimulating protein breakdown and inhibiting protein synthesis. Signaling pathways that regulate muscle protein synthesis at the translational level are inhibited by glucocorticoids. Glucocorticoids increase the expression and activity of the ubiquitin-proteasome pathway, a major proteolytic mechanism of muscle atrophy. The expression and activity of muscle wasting-related transcription factors, including C/EBPβ and δ and Forkhead box 0 1, 3, and 4, as well as the nuclear cofactor p300, are up-regulated by glucocorticoid excess. Conclusions: Muscle wasting in various catabolic conditions is, at least in part, regulated by glucocorticoids. The role of glucocorticoids in muscle wasting is complex and reflects regulation at the molecular level of multiple mechanisms influencing both synthesis and degradation of muscle proteins. |
Databáze: | OpenAIRE |
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