Insulin-like growth factor-I blocks dexamethasone-induced protein degradation in cultured myotubes by inhibiting multiple proteolytic pathways: 2002 ABA paper.
In previous studies, insulin-like growth factor-I (IGF-I) inhibited glucocorticoid-induced muscle protein breakdown, but the intracellular mechanisms of this effect of IGF-I are not well understood. The purpose of the present study was to test the hypothesis that IGF-I inhibits multiple proteolytic pathways in dexamethasone-treated cultured L6 myotubes. Myotubes were treated with 1 microM dexamethasone for 6 hours in the absence or presence of 0.1 microg/ml of IGF-I. Protein degradation was determined by measuring the release of trichloroacetic acid-soluble radioactivity from proteins prelabeled with 3H-tyrosine. The contribution of lysosomal, proteasomal-dependent, and calpain-dependent proteolysis to the inhibitory effect of IGF-I on protein degradation was assessed by using inhibitors of the individual proteolytic pathways (methylamine, beta-lactone, and E64, respectively). In addition, the influence of IGF-I on cathepsin B, proteasome, and calpain activities was determined. Treatment of L6 myotubes with dexamethasone resulted in an approximately 20% increase in protein degradation. This effect of dexamethasone was completely blocked by IGF-I. When the different protease inhibitors were used, results showed that IGF-I inhibited lysosomal, proteasomal-dependent, and calpain-dependent proteolysis by 70, 44, and 41%, respectively. Additionally, IGF-I blocked the dexamethasone-induced increase in cathepsin B, proteasome, and calpain activities. The present results suggest that IGF-I inhibits glucocorticoid-induced muscle proteolysis by blocking multiple proteolytic pathways.
Li
Bing-Guo
BG
Shriners Hospitals for Children-Cincinnati Burns Hospital, Cincinnati, Ohio 45229, USA.
Hasselgren
Per-Olof
PO
Fang
Cheng-Hui
CH
Warden
Glenn D
GD
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats
D009124:Muscle Proteins; D011480:Protease Inhibitors; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone