title: Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: analysis by microarray.
abstract: Administration of glucocorticoids results in hypertension, cardiac hypertrophy, and general myopathy. The present study analyzed the acute effect of dexamethasone (0.5 mg/100 g for 3 days) or dexamethasone plus insulin-like growth factor-1 (0.35 mg/100 g for 3 days) on differential gene expression in the gastrocnemius muscle and the left ventricular myocardium of rats. Dexamethasone induced atrophy of gastrocnemius muscle. Cathepsin L, and not ubiquitin, was the earliest mediator of skeletal muscle proteolysis induced by dexamethasone. Insulin-like growth factor-1 reversed gastrocnemius muscle mass, and deleted a part of downregulated genes by dexamethasone. On the other hand, dexamethasone administration did not result in cardiac hypertrophy or hypertension. Only prostaglandin D synthase gene was upregulated by dexamethasone in myocardium, and genes related to extracellular matrix and proteinase inhibitor were downregulated. Molecular alteration for hypertrophy might have initiated. Dexamethasone-induced proteolysis and reversal with insulin-like growth factor-1 occurred rapidly in skeletal muscle; but was relatively delayed in the myocardium.
authors: Department of Cardiovascular Dynamics, Research Institute, National Cardiovascular Center, Suita, Japan. kkoma@hsp.ncvc.go.jp
authors: Kazuo
authors: K
authors: Komamura
authors: Hiroko
authors: H
authors: Shirotani-Ikejima
authors: Rie
authors: R
authors: Tatsumi
authors: Yuko
authors: Y
authors: Tsujita-Kuroda
authors: Masafumi
authors: M
authors: Kitakaze
authors: Kunio
authors: K
authors: Miyatake
authors: Kenji
authors: K
authors: Sunagawa
authors: Toshiyuki
authors: T
authors: Miyata
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects; D015870:Gene Expression; D005938:Glucocorticoids / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone