Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Korea.
Department of Marine Bio-Materials & Aquaculture, Pukyong National University, Busan 48513, Korea.
Mar Drugs. 2019 May 11;17(5):284. doi: 10.3390/md17050284.
Dexamethasone (DEX), a synthetic glucocorticoid, causes skeletal muscle atrophy. This study examined the protective effects of peptide (PYP15) against DEX-induced myotube atrophy and its association with insulin-like growth factor-I (IGF-I) and the Akt/mammalian target of rapamycin (mTOR)-forkhead box O (FoxO) signaling pathway. To elucidate the molecular mechanisms underlying the effects of PYP15 on DEX-induced myotube atrophy, C2C12 myotubes were treated for 24 h with 100 μM DEX in the presence or absence of 500 ng/mL PYP15. Cell viability assays revealed no PYP15 toxicity in C2C12 myotubes. PYP15 activated the insulin-like growth factor-I receptor (IGF-IR) and Akt-mTORC1 signaling pathway in DEX-induced myotube atrophy. In addition, PYP15 markedly downregulated the nuclear translocation of transcription factors FoxO1 and FoxO3a, and inhibited 20S proteasome activity. Furthermore, PYP15 inhibited the autophagy-lysosomal pathway in DEX-stimulated myotube atrophy. Our findings suggest that PYP15 treatment protected against myotube atrophy by regulating IGF-I and the Akt-mTORC1-FoxO signaling pathway in skeletal muscle. Therefore, PYP15 treatment appears to exert protective effects against skeletal muscle atrophy.
地塞米松（DEX），一种合成的糖皮质激素，会导致骨骼肌萎缩。本研究探讨了肽（PYP15）对 DEX 诱导的肌管萎缩的保护作用及其与胰岛素样生长因子-I（IGF-I）和 Akt/哺乳动物雷帕霉素靶蛋白（mTOR）-叉头框 O（FoxO）信号通路的关系。为了阐明 PYP15 对 DEX 诱导的肌管萎缩的影响的分子机制，用 100 μM DEX 处理 C2C12 肌管 24 h，同时存在或不存在 500ng/mL PYP15。细胞活力测定显示 C2C12 肌管中 PYP15 没有毒性。PYP15 在 DEX 诱导的肌管萎缩中激活胰岛素样生长因子-I 受体（IGF-IR）和 Akt-mTORC1 信号通路。此外，PYP15 显著下调转录因子 FoxO1 和 FoxO3a 的核转位，并抑制 20S 蛋白酶体活性。此外，PYP15 抑制 DEX 刺激的肌管萎缩中的自噬-溶酶体途径。我们的研究结果表明，PYP15 通过调节骨骼肌中的 IGF-I 和 Akt-mTORC1-FoxO 信号通路来防止肌管萎缩。因此，PYP15 治疗似乎对骨骼肌萎缩具有保护作用。
