Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 537, Issue 1, Pages 21-30Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2013.06.006
Keywords
Celastrol; Countermeasure; Dexamethasone; HSF1; HSP72; Muscle atrophy
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Funding
- Korea Aerospace Research Institute
- Japan Aerospace Exploration Agency
- research grant Fundamental Study of Manned Space Technology for Microgravity Environment Utilization
- Korea Aerospace Research Institute (KARI) [FR13350W01]
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Celastrol (CEL) is known as a potent inducer of heat shock protein (HSP) in non-muscle cells and exhibits cytoprotective function and inhibitory effects on proteasome and glucocorticoid receptor activities. To investigate an anti-atrophic effect of CEL on skeletal muscle cells, C2C12 myotubes were treated with 150 mu M dexamethasone (DEX) for 24 h and 1.5 mu M CEL was added for the last 6 h during the 24 h DEX treatment. Compared to the control, the myotube diameter was reduced by a factor of 0.30 by DEX, but CEL treatment almost abrogated the DEX-induced atrophy. CEL treatment also increased expression of HSP72 and phosphorylation of heat shock transcription factor 1 (p-HSF1) 11-fold and 3.4-fold, respectively, as well as accumulation of p-HSF1 in the nucleus. Furthermore, CEL treatment elevated activities of Akt1, p70/S6K and ERK1/2 2.0- to 4.4-fold whereas DEX had no effect on these signaling activities. Inhibition of Akt1 and ERK1/2 pathways by specific inhibitors confirmed CEL-induced anti-atrophic effect. Moreover, DEX-mediated downregulation of FoxO3 phosphorylation and upregulation of MuRF1 expression and proteasome activity were abrogated by CEL treatment. These results demonstrate a novel anti-atrophic function of CEL in muscle cells via both activation of protein anabolic signals and suppression of catabolic signaling activities. (C) 2013 Elsevier Inc. All rights reserved.
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