Inhibition of C2C12 myotube atrophy by a novel HSP70 inducer, celastrol, via activation of Akt1 and ERK1/2 pathways

Taesik Gwag, Kyoungsook Park, Eunjung Kim, Chaeyeon Son, Junsoo Park, Takeshi Nikawa, Inho Choi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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 lM dexamethasone (DEX) for 24 h and 1.5 lM 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 antiatrophic function of CEL in muscle cells via both activation of protein anabolic signals and suppression of catabolic signaling activities.

Original languageEnglish
Pages (from-to)21-30
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume537
Issue number1
DOIs
Publication statusPublished - 2013

Bibliographical note

Funding Information:
We are grateful to Ms. Sim NamKoong at Yonsei University and collaborators from Korea Aerospace Research Institute and Japan Aerospace Exploration Agency for their support for this project. We also thank three anonymous reviewers for their kind comments that greatly improved this manuscript. This research was supported by the research grant “Fundamental Study of Manned Space Technology for Microgravity Environment Utilization” funded by Korea Aerospace Research Institute (KARI) (FR13350W01).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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