Spermidine-Activated Satellite Cells Are Associated with Hypoacetylation in ACVR2B and Smad3 Binding to Myogenic Genes in Mice,Journal of Agricultural and Food Chemistry

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Spermidine-Activated Satellite Cells Are Associated with Hypoacetylation in ACVR2B and Smad3 Binding to Myogenic Genes in Mice
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-01-04 00:00:00 , DOI: 10.1021/acs.jafc.7b04482
Luchu Zhang ₁ , Huiying Gong ₁ , Qinwei Sun ₁ , Ruqian Zhao _{1,

2} , Yimin Jia _{1,

2}

Affiliation

Spermidine is an acetyltransferase inhibitor and a specific inducer of autophagy. Recently, spermidine is identified as a potential therapeutic agent for age-related muscle atrophy and inherited myopathies. However, the effect of spermidine on nonpathological skeletal muscle remains unclear. In this study, long-term spermidine administration in mice lowered the mean cross-sectional area of the gastrocnemius muscle and reduced the expression of myosin heavy chain isoforms in the muscle, which was associated with ubiquitination. Moreover, spermidine supplementation induced autophagy in satellite cells and enhanced satellite cell proliferation. ChIP assay revealed that spermidine repressed H3K56ac in the promoter of ACVR2B and lowered the binding affinity of Smad3 to the promoters of Myf5 and MyoD. Altogether, our results indicate that long-term administration of spermidine can activate satellite cells, as well as enhance autophagy, eventually resulting in muscle atrophy. In addition, H3K56ac and Smad3 emerged as key determinants of satellite cell activation.

中文翻译：

亚精胺激活的卫星细胞与ACVR2B和Smad3绑定到小鼠的成肌基因的hypoacetylation相关联。

亚精胺是乙酰转移酶抑制剂和自噬的特异性诱导剂。最近，亚精胺被确定为与年龄有关的肌肉萎缩和遗传性肌病的潜在治疗剂。然而，亚精胺对非病理性骨骼肌的作用仍不清楚。在这项研究中，长期给予小鼠亚精胺可降低腓肠肌的平均横截面积，并减少肌肉中肌球蛋白重链同工型的表达，这与泛素化有关。此外，亚精胺的补充在卫星细胞中诱导自噬并增强卫星细胞的增殖。ChIP分析显示亚精胺抑制ACVR2B启动子中的H3K56ac，并降低Smad3与Myf5和MyoD启动子的结合亲和力。共，我们的结果表明，长期服用亚精胺可以激活卫星细胞，并增强自噬，最终导致肌肉萎缩。此外，H3K56ac和Smad3成为卫星细胞激活的关键决定因素。

更新日期：2018-01-04

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