Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro

J Cell Physiol. 2017 Mar;232(3):650-664. doi: 10.1002/jcp.25609. Epub 2016 Oct 19.

Abstract

It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid-induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid-induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel-like factor 15 (KLF15). Heat stress recovered the dexamethasone-induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress-induced protection against glucocorticoid-induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650-664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.

MeSH terms

  • Animals
  • Cell Line
  • Dexamethasone / adverse effects*
  • Gene Expression Regulation / drug effects
  • Glycogen Synthase Kinase 3 beta
  • HSP72 Heat-Shock Proteins / metabolism
  • Heat-Shock Response / drug effects*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Atrophy / chemically induced*
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects*
  • Time Factors

Substances

  • HSP72 Heat-Shock Proteins
  • Muscle Proteins
  • RNA, Messenger
  • Dexamethasone
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa