title: Effect of irradiation on Akt signaling in atrophying skeletal muscle.
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 AktT308phosphorylation, whereas HS+IRR resulted in increased AktT308phosphorylation above baseline. HS resulted in reduced AktS473phosphorylation, which was rescued by HS+IRR. Interestingly, IRR alone resulted in increased phosphorylation of AktS473, but not that of AktT308HS 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.
authors: Integrative Muscle Biology Laboratory, Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
authors: Dennis K
authors: DK
authors: Fix
authors: Integrative Muscle Biology Laboratory, Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
authors: Justin P
authors: JP
authors: Hardee
authors: Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
authors: Ted A
authors: TA
authors: Bateman
authors: Integrative Muscle Biology Laboratory, Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and carsonj@mailbox.sc.edu.
authors: James A
authors: JA
authors: Carson
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000503:physiopathology* / Q000528:radiation effects*; D009133:Muscular Atrophy / Q000503:physiopathology*; D010766:Phosphorylation / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011829:Radiation Dosage; D000069079:Radiation Exposure; D015398:Signal Transduction / Q000528:radiation effects*
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: MuRF-1; atrophy; mTORC1; microgravity; protein turnover; unloading