Semaphorin-3A通过调节自噬减轻心肌肥厚

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Yu Sun, Jin Dong, Xiaohong Chai, Jingping Wang, Bao Li, Jinjing Yang
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引用次数: 0

摘要

心脏肥大以心肌细胞增大为特征,是心脏对某些肥大刺激的一种适应性反应;然而,长期肥大会导致心脏功能障碍,并最终引起心力衰竭。本研究利用异丙肾上腺素(ISO)诱导的 H9c2 细胞模型,评估了神经化学抑制剂 semaphorin-3A(Sema3A)在心脏肥大中的作用。用罗丹明-类黄酮染色细胞以评估细胞表面积,并进行逆转录-定量 PCR,以量化 Sema3A、脑钠肽因子(BNF)和β-肌球蛋白重链(β-MHC)的 mRNA 表达水平。用 Western 印迹法对自噬相关蛋白轻链 3(LC3)、p62 和 Beclin-1,以及 Akt/mTOR 信号通路相关蛋白 Akt、磷酸化(p)-Akt、mTOR、p-mTOR、4E 结合蛋白 1(4EBP1)和 p-4EBP1 的蛋白表达水平进行了半定量分析。对H9c2细胞施用雷帕霉素(一种典型的自噬诱导剂)以阐明Sema3A的调控机制。结果表明,用ISO处理H9c2心肌细胞24小时后,细胞表面积明显增加,BNF和β-MHC mRNA表达水平升高,LC3II/I比值和Beclin-1蛋白表达水平升高,p62蛋白表达水平明显降低。Sema3A过表达可改善ISO诱导的H9c2细胞肥大,表现为细胞表面积减少,BNF和β-MHC mRNA表达水平降低。此外,Sema3A的过表达抑制了ISO诱导的H9c2细胞自噬,表现为LC3II/I比值和Beclin-1蛋白表达水平的降低以及p62蛋白表达水平的升高。自噬激活剂雷帕霉素部分抑制了Sema3A对ISO诱导的肥大的保护作用。Sema3A的过表达抑制了ISO诱导的p-Akt、mTOR及其下游靶标4EBP1蛋白表达水平的下降。总之,这些结果表明,Sema3A可通过Akt/mTOR信号通路抑制自噬,从而防止ISO诱导的心脏肥大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Semaphorin‑3A alleviates cardiac hypertrophy by regulating autophagy.
Cardiac hypertrophy, characterized by cardiomyocyte enlargement, is an adaptive response of the heart to certain hypertrophic stimuli; however, prolonged hypertrophy results in cardiac dysfunction and can ultimately cause heart failure. The present study evaluated the role of semaphorin-3A (Sema3A), a neurochemical inhibitor, in cardiac hypertrophy, utilizing an isoproterenol (ISO) induced H9c2 cell model. Cells were stained with rhodamine-phalloidin to assess the cell surface area and reverse transcription-quantitative PCR was performed to quantify mRNA expression levels of Sema3A, brain natriuretic factor (BNF) and β-myosin heavy chain (β-MHC). The protein expression levels of the autophagy-related proteins light chain 3 (LC3), p62 and Beclin-1, and the Akt/mTOR signaling pathway associated proteins Akt, phosphorylated (p)-Akt, mTOR, p-mTOR, 4E-binding protein 1 (4EBP1) and p-4EBP1 were semi-quantified using western blotting. Rapamycin, a canonical autophagy inducer, was administered to H9c2 cells to elucidate the regulatory mechanism of Sema3A. The results indicated significantly increased cell surface area and elevated BNF and β-MHC mRNA expression levels, increased LC3II/I ratio and Beclin-1 protein expression levels and significantly decreased p62 protein expression levels after treatment of H9c2 cardiomyocytes with ISO for 24 h. Sema3A overexpression improved ISO-induced hypertrophy in H9c2 cells, indicated by decreased cell surface area and reduced BNF and β-MHC mRNA expression levels. Moreover, Sema3A overexpression inhibited ISO-induced autophagy in H9c2 cells, indicated by decreased LC3II/I ratio and Beclin-1 protein expression levels and increased p62 protein expression levels. The autophagy activator rapamycin partially inhibited the protective effect of Sema3A on ISO-induced hypertrophy. Sema3A overexpression suppressed the decrease of the protein expression levels of p-Akt, mTOR and their downstream target 4EBP1, which is induced by ISO. Collectively, these results suggested Sema3A prevented ISO-induced cardiac hypertrophy by inhibiting autophagy via the Akt/mTOR signaling pathway.
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来源期刊
Experimental and therapeutic medicine
Experimental and therapeutic medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
1.50
自引率
0.00%
发文量
570
审稿时长
1 months
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