Astragaloside IV protects cardiomyocytes from hypoxia-induced injury by down-regulation of lncRNA GAS5 (Retracted article. See vol. 153, 2022)
Astragaloside IV protects cardiomyocytes from hypoxia-induced injury by down-regulation of lncRNA GAS5 (Retracted article. See vol. 153, 2022)
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DOI：
10.1016/j.biopha.2019.109028
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发表时间：
2019-08-01
影响因子：
7.5
通讯作者：
Leng, Ji-Yan
中科院分区：
文献类型：
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作者：
Du, Jian;Liu, Jia;Leng, Ji-Yan
背景资料：对黄芪甲苷（AS-IV）心血管保护作用的调节机制认识不足，限制了AS-IV在心力衰竭中的临床应用。缺氧是心力衰竭进展的重要刺激因素。方法：采用CCK-8法和流式细胞仪分别检测缺氧处理后H9 c2细胞的存活率和凋亡细胞数。Western blot检测细胞增殖和凋亡相关蛋白的表达。探讨AS-IV对缺氧诱导的细胞损伤的影响，并通过RT-qPCR检测AS-IV处理后lncRNA生长阻滞特异性5（GAS 5）水平的变化。随后证实AS-IV是否通过lncRNA GAS 5影响缺氧处理的H9 c2细胞。结果：AS-IV可抑制缺氧引起的细胞存活率下降、凋亡细胞增多以及与细胞增殖和凋亡相关的蛋白表达。结果表明，AS-IV可下调lncRNA GASS的表达，提示AS-IV可能通过lncRNA GAS 5影响缺氧诱导的H9 c2细胞。结论：AS-IV通过下调H9 c2细胞lncRNA GAS 5的表达，保护H9 c2细胞免受缺氧损伤。此外，AS-IV可能通过激活PI 3 K/mTOR通路抑制lncRNA GAS 5的表达。
Background: Poor understanding of the regulatory mechanisms of astragaloside IV (AS-IV) in cardiovascular protection limits clinical application of AS-IV in heart failure. Hypoxia is an important stimulus in the progression of heart failure. We investigated the role of AS-IV in hypoxia-treated cardiomyoblast H9c2 cells.Methods: Cell viability and apoptotic cells in hypoxia-treated H9c2 cells were detected by CCK-8 assay and flow cytometry, respectively. Expression of proteins associated with proliferation and apoptosis was measured by Western blot. Then effects of AS-IV on hypoxia-induced cell injury were explored, and the alteration of lncRNA growth arrest specific 5 (GAS5) level under AS-IV treatment was determined by RT-qPCR. Whether AS-IV affected hypoxia-treated H9c2 cells via lncRNA GAS5 was subsequently testified. Besides, whether AS-IV regulated lncRNA GAS5 expression was via modulating the PI3K/mTOR pathway was investigated.Results: Hypoxia-induced decreasing cell viability, increasing apoptotic cells, and proteins associated with proliferation and apoptosis were all attenuated by AS-IV treatments. Then, we found that lncRNA GASS expression was down-regulated by AS-IV treatment, and AS-IV might affect hypoxia-stimulated H9c2 cells through lncRNA GAS5. Finally, we found that inhibition of PI3K/mTOR or mTOR could reverse the AS-IV-induced downregulation of lncRNA GAS5 in H9c2 cells.Conclusion: AS-IV protected H9c2 cells against hypoxia through down-regulating lncRNA GAS5. Besides, AS-IV might repress lncRNA GAS5 expression via activation of the PI3K/mTOR pathway.