AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling

Douglas R. Bolster, Stephen J. Crozier, Scot R. Kimball, Leonard S. Jefferson

Research output: Contribution to journalArticlepeer-review

625 Scopus citations

Abstract

AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to modulate glucose uptake and fatty acid oxidation in skeletal muscle. Given that protein synthesis is a high energy-consuming process, it may be transiently depressed during cellular energy stress. Thus, the intent of this investigation was to examine whether AMPK activation modulates the translational control of protein synthesis in skeletal muscle. Injections of 5-aminoimidazole-4-carboxamide 1-β-D-ri-bonucleoside (AICAR) were used to activate AMPK in male rats. The activity of α1 AMPK remained unchanged in gastrocnemius muscle from AICAR-treated animals compared with controls, whereas α2 AMPK activity was significantly increased (51%). AICAR treatment resulted in a reduction in protein synthesis to 45% of the control value. This depression was associated with decreased activation of protein kinases in the mammalian target of rapamycin (mTOR) signal transduction pathway as evidenced by reduced phosphorylation of protein kinase B on Ser473, MTOR on Ser2448, ribosomal protein S6 kinase on Thr389, and eukaryotic initiation factor eIF4E-binding protein on Thr37. A reduction in eIF4E associated with eIF4G to 10% of the control value was also noted. In contrast, eIF2B activity remained unchanged in response to AICAR treatment and therefore would not appear to contribute to the depression in protein synthesis. This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in response to AMPK activation.

Original languageEnglish (US)
Pages (from-to)23977-23980
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number27
DOIs
StatePublished - Jul 5 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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