skeletal muscle 11beta-hsd1 controls glucocorticoid-induced proteolysis and expression of e3 ubiquitin ligases atrogin-1 and murf-1骨骼肌11 beta-hsd1控制激素性蛋白质水解和e3泛素连接酶的表达atrogin-1 murf-1.pdfVIP

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skeletal muscle 11beta-hsd1 controls glucocorticoid-induced proteolysis and expression of e3 ubiquitin ligases atrogin-1 and murf-1骨骼肌11 beta-hsd1控制激素性蛋白质水解和e3泛素连接酶的表达atrogin-1 murf-1.pdf

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skeletal muscle 11beta-hsd1 controls glucocorticoid-induced proteolysis and expression of e3 ubiquitin ligases atrogin-1 and murf-1骨骼肌11 beta-hsd1控制激素性蛋白质水解和e3泛素连接酶的表达atrogin-1 murf-1

Skeletal Muscle 11beta-HSD1 Controls Glucocorticoid- Induced Proteolysis and Expression of E3 Ubiquitin Ligases Atrogin-1 and MuRF-1 1 1 1 2 2 3 Katrin Biedasek , Janin Andres , Knut Mai , Stephanie Adams , Simone Spuler , Jens Fielitz , Joachim Spranger1* ´ ¨ 1 Department of Endocrinology, Diabetes and Nutrition, Charite-Universitatsmedizin Berlin, Berlin, Germany, 2 Muscle Research Unit, Experimental and Clinical Research ´ ¨ ´ ¨ Center, Charite-Universitatsmedizin Berlin, Berlin, Germany, 3 Department of Cardiology and Experimental and Clinical Research Center, Charite-Universitatsmedizin Berlin, Berlin, Germany Abstract Recent studies demonstrated expression and activity of the intracellular cortisone-cortisol shuttle 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in skeletal muscle and inhibition of 11beta-HSD1 in muscle cells improved insulin sensitivity. Glucocorticoids induce muscle atrophy via increased expression of the E3 ubiquitin ligases Atrogin-1 (Muscle Atrophy F-box (MAFbx)) and MuRF-1 (Muscle RING-Finger-1). We hypothesized that 11beta-HSD1 controls glucocorticoid- induced expression of atrophy E3 ubiquitin ligases in skeletal muscle. Primary human myoblasts were generated from healthy volunteers. 11beta-HSD1-dependent protein degradation was analyzed by [3H]-tyrosine release assay. RT-PCR was used to determine mRNA expression of E3 ubiquitin ligases and 11beta-HSD1 activity was measured by conversion of radioactively labeled [3