Effect of irradiation on Akt signaling in atrophying skeletal muscle

Dennis K. Fix, Justin P. Hardee, Ted A. Bateman, James Carson

Research output: Contribution to journalArticle

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Abstract

Muscle irradiation (IRR) exposure can accompany unloading during spaceflight or cancer treatment, and this has been shown to be sufficient by itself to induce skeletal muscle signaling associated with a remodeling response. Although protein kinase B/Akt has an established role in the regulation of muscle growth and metabolism, there is a limited understanding of how Akt signaling in unloaded skeletal muscle is affected by IRR. Therefore, we examined the combined effects of acute IRR and short-term unloading on muscle Akt signaling. Female C57BL/6 mice were subjected to load bearing or hindlimb suspension (HS) for 5 days (n = 6/group). A single, unilateral hindlimb IRR dose (0.5 Gy X-ray) was administered on day 3. Gastrocnemius muscle protein expression was examined. HS resulted in decreased AktT308 phosphorylation, whereas HS-IRR resulted in increased AktT308 phosphorylation above baseline. HS resulted in reduced AktS473 phosphorylation, which was rescued by HS-IRR. Interestingly, IRR alone resulted in increased phosphorylation of AktS473, but not that of AktT308. HS resulted in decreased mTORC1 signaling, and this suppression was not altered by IRR. Both IRR and HS resulted in increased MuRF-1 expression, whereas atrogin-1 expression was not affected by either condition. These results demonstrate that either IRR alone or when combined with HS can differentially affect Akt phosphorylation, but IRR did not disrupt suppressed mTORC1 signaling by HS. Collectively, these findings highlight that a single IRR dose is sufficient to disrupt the regulation of Akt signaling in atrophying skeletal muscle.

Original languageEnglish (US)
Pages (from-to)917-924
Number of pages8
JournalJournal of applied physiology
Volume121
Issue number4
DOIs
StatePublished - Oct 1 2016

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Hindlimb Suspension
Skeletal Muscle
Phosphorylation
Muscles
Space Flight
Proto-Oncogene Proteins c-akt
Muscle Proteins
Weight-Bearing
Hindlimb
Inbred C57BL Mouse
X-Rays

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Effect of irradiation on Akt signaling in atrophying skeletal muscle. / Fix, Dennis K.; Hardee, Justin P.; Bateman, Ted A.; Carson, James.

In: Journal of applied physiology, Vol. 121, No. 4, 01.10.2016, p. 917-924.

Research output: Contribution to journalArticle

Fix, Dennis K. ; Hardee, Justin P. ; Bateman, Ted A. ; Carson, James. / Effect of irradiation on Akt signaling in atrophying skeletal muscle. In: Journal of applied physiology. 2016 ; Vol. 121, No. 4. pp. 917-924.
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