Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

Song Gao, James Carson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLCderived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes.

Original languageEnglish (US)
Pages (from-to)C66-C79
JournalAmerican Journal of Physiology - Cell Physiology
Volume310
Issue number1
DOIs
StatePublished - Jan 1 2016

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Lewis Lung Carcinoma
Skeletal Muscle Fibers
Proteins
AMP-Activated Protein Kinases
Glycoproteins
Phosphorylation
Leukemia Inhibitory Factor
Muscle Proteins
mechanistic target of rapamycin complex 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes. / Gao, Song; Carson, James.

In: American Journal of Physiology - Cell Physiology, Vol. 310, No. 1, 01.01.2016, p. C66-C79.

Research output: Contribution to journalArticle

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