Zhang Luchu, Gong Huiying, Sun Qinwei, Zhao Ruqian, Jia Yimin
Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University , Nanjing 210095, P. R. China.
Quality and Safety Control, Jiangsu Collaborative Innovation Center of Meat Production and Processing , Nanjing 210095, P. R. China.
J Agric Food Chem. 2018 Jan 17;66(2):540-550. doi: 10.1021/acs.jafc.7b04482. Epub 2018 Jan 4.
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.
亚精胺是一种乙酰转移酶抑制剂和自噬的特异性诱导剂。最近，亚精胺被确定为一种治疗与年龄相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影响仍不清楚。在本研究中，长期给小鼠施用亚精胺降低了腓肠肌的平均横截面积，并降低了肌肉中肌球蛋白重链亚型的表达，这与泛素化有关。此外，补充亚精胺可诱导卫星细胞自噬并增强卫星细胞增殖。染色质免疫沉淀分析表明，亚精胺抑制了ACVR2B启动子中的H3K56ac，并降低了Smad3与Myf5和MyoD启动子的结合亲和力。总之，我们的结果表明，长期施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是卫星细胞激活的关键决定因素。
