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首页> 外文期刊>Molecular medicine reports >Sanggenon C protects against cardiomyocyte hypoxia injury by increasing autophagy
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Sanggenon C protects against cardiomyocyte hypoxia injury by increasing autophagy

机译:Sanggenon C通过增加自噬抗心肌细胞缺氧损伤

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摘要

Sanggenon C is isolated from Morus alba, a plant that has been used for anti-inflammatory purposes in Oriental medicine. Little is known about the effect of Sanggenon C on cardiomyocyte hypoxia injury. This study, using H9c2 rat cardiomyoblasts, was designed to determine the effects of Sanggenon C on cardiomyocyte hypoxia injury. Inflammatory cytokine levels were measured by reverse transcription-polymerase chain reaction, reactive oxygen species were measured by 2',7'-dichlorofluorescin diacetate fluorescent probe, autophagy was detected using the LC3II/I ratio and cell apoptosis was detected by TUNEL staining. The molecular mechanisms underlying Sanggenon C-induced cyto-protection were also determined by western blotting, especially the possible involvement of autophagy and AMP-activated protein kinase (AMPK). Results indicated that samples pretreated with different concentrations of Sanggenon C (1, 10 and 100 mu M) reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor a, interleukin (IL)-1 and IL-6, under hypoxia. The beneficial effects of Sanggenon C were also associated with reduced levels of reactive oxygen species generation and increased levels of antioxidant nitric oxide and superoxide dismutase. Sanggenon C enhanced hypoxia-induced autophagy as evidenced by the increased expression levels of autophagy-associated proteins Beclin and autophagy related 5 as well as the decreased the accumulation of p62, and increased the LC3II/I ratio. Sanggenon C also reduced hypoxia-induced apoptosis as detected by TUNEL staining and the expression of Bcl-2 proteins. The beneficial effects of Sanggenon C were associated with enhanced activation level of AMPK alpha and suppressed hypoxia-induced mechanistic target of rapamycin (mTOR) and forkhead box O3a (FOXO3a) phosphorylation. The AMPK inhibitor Compound C (CpC) was used, and the anti-apoptotic and pro-autophagy effects of Sanggenon C in response to hypoxia were abolished by CpC. In conclusion, the current study demonstrated that Sanggenon C possessed direct cytoprotective effects against hypoxia injury in cardiac cells via signaling mechanisms involving the activation of AMPK and concomitant inhibition of mTOR and FOXO3a.
机译:Sanggenon C是从Morus Alba分离的,该植物已被用于东方药物的抗炎目的。关于Sanggenon C对心肌细胞缺氧损伤的影响很少。本研究旨在使用H9C2大鼠心肌细胞设计,以确定Sanggenon C对心肌细胞缺氧损伤的影响。通过逆转录 - 聚合酶链反应测量炎症细胞因子水平,通过2'测量反应性氧物质,7'-二氯荧光蛋白杂液荧光探针,使用LC3II / I比检测自噬,并通过TUNEL染色检测细胞凋亡。 Sanggenon C诱导的细胞保护的分子机制也通过蛋白质印迹,尤其是自噬和AMP-活化的蛋白激酶(AMPK)的可能涉及。结果表明,用不同浓度的Sanggenon C(1,10和100μm)预处理的样品降低了缺氧下肿瘤坏死因子A,白细胞介素(IL)-1和IL-6的促炎细胞因子的表达水平。 Sanggenon C的有益效果也与降低的反应性氧物质产生和抗氧化型一氧化氮和超氧化物歧化酶的水平降低有关。 SangGenon C增强缺氧诱导的自噬如,通过增加的自噬相关蛋白BENCLIN和自噬相关5的表达水平以及P62的积累率降低,并增加了LC3II / I比率。 Sanggenon C也减少了由TUNEL染色和BCL-2蛋白的表达检测到的缺氧诱导的细胞凋亡。 SangGenon C的有益效果与增强的AMPKα激活水平相关,抑制雷帕霉素(MTOR)和FORKHEAD盒O3A(FOXO3A)磷酸化的缺氧诱导的机械靶。使用AMPK抑制剂化合物C(CPC),并通过CPC废除了Sanggenon C响应缺氧的抗凋亡和亲自噬作用。总之,目前的研究证明,SangGenon C通过涉及激活AMPK和伴随MTOR和FOXO3A的信号传导机制对心脏细胞的缺氧损伤具有直接的细胞保护作用。

著录项

  • 来源
    《Molecular medicine reports》 |2017年第3期|共7页
  • 作者单位

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Zhengzhou Univ Dept Cardiol Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R China;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

    Nanjing Med Univ Huaian Peoples Hosp 1 Dept Cardiol 6 Beijing Rd West Huaian 223300 Jiangsu;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
  • 关键词

    Sanggenon C; cardiomyocyte; hypoxia; autophagy; AMP-activated protein kinase alpha;

    机译:Sanggenon C;心肌细胞;缺氧;自噬;AMP活化蛋白激酶α;

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