Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: analysis by microarray.
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.
Komamura
Kazuo
K
Department of Cardiovascular Dynamics, Research Institute, National Cardiovascular Center, Suita, Japan. kkoma@hsp.ncvc.go.jp
Shirotani-Ikejima
Hiroko
H
Tatsumi
Rie
R
Tsujita-Kuroda
Yuko
Y
Kitakaze
Masafumi
M
Miyatake
Kunio
K
Sunagawa
Kenji
K
Miyata
Toshiyuki
T
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
D005938:Glucocorticoids; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone