Fix Dennis K, Hardee Justin P, Bateman Ted A, Carson James A
Integrative Muscle Biology Laboratory, Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
J Appl Physiol (1985). 2016 Oct 1;121(4):917-924. doi: 10.1152/japplphysiol.00218.2016. Epub 2016 Aug 25.
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 Akt phosphorylation, whereas HS+IRR resulted in increased Akt phosphorylation above baseline. HS resulted in reduced Akt phosphorylation, which was rescued by HS+IRR. Interestingly, IRR alone resulted in increased phosphorylation of Akt, but not that of Akt 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.
肌肉辐射（IRR）暴露可能伴随太空飞行或癌症治疗期间的失重状态，并且已证明其本身足以诱导与重塑反应相关的骨骼肌信号传导。尽管蛋白激酶B/Akt在肌肉生长和代谢的调节中已确立作用，但对于失重状态下骨骼肌中Akt信号传导如何受IRR影响的了解有限。因此，我们研究了急性IRR和短期失重对肌肉Akt信号传导的联合作用。将雌性C57BL/6小鼠进行承重或后肢悬吊（HS）处理5天（每组n = 6）。在第3天给予单次单侧后肢IRR剂量（0.5 Gy X射线），并检测腓肠肌蛋白表达。HS导致Akt磷酸化降低，而HS+IRR导致Akt磷酸化高于基线水平。HS导致Akt磷酸化降低，而HS+IRR使其恢复。有趣的是，单独的IRR导致Akt磷酸化增加，但不影响Akt。HS导致mTORC1信号传导降低，且这种抑制不受IRR影响。IRR和HS均导致MuRF-1表达增加，而atrogin-1表达在两种情况下均未受影响。这些结果表明，单独的IRR或与HS联合使用均可不同程度地影响Akt磷酸化，但IRR不会破坏HS对mTORC1信号传导的抑制作用。总体而言，这些发现突出表明单次IRR剂量足以破坏萎缩骨骼肌中Akt信号传导的调节。
