Notch1 provides myocardial protection by improving mitochondrial quality control
Notch1 provides myocardial protection by improving mitochondrial quality control
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Notch1 通过改善线粒体质量控制来提供心肌保护。
DOI：
10.1002/jcp.27892
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发表时间：
2019
影响因子：
5.6
通讯作者：
Ji-chun Liu
中科院分区：
文献类型：
--
作者：
Xue-liang Zhou;Xia Wu;Qi-rong Xu;Rong-rong Zhu;Hua Xu;Yun-yun Li;Sheng Liu;Huang Huang;Xinping Xu;Li Wan;Qi-cai Wu;Ji-chun Liu
线粒体质量控制是心肌保护的新目标。 Notch信号在心脏发育、成熟和修复中发挥着重要作用。然而，Notch 在心肌线粒体质量控制中的作用仍然难以捉摸。在本研究中，我们分离大鼠心肌细胞并建立心肌缺血再灌注损伤（IRI）模型。我们通过重组腺病毒 Ad-N1ICD 和 Ad-shN1ICD 感染来调节心肌细胞中的 Notch1 表达水平。我们发现IR降低了心肌细胞的活力，但Notch1过度表达增加了暴露于IRI的心肌细胞的活力。此外，Notch1 过表达可改善 ATP 生成，增加线粒体融合并减少线粒体裂变，并抑制暴露于 IRI 的心肌细胞的线粒体自噬。然而，N1ICD 敲除导致了相反的效果。 Notch1的心肌保护作用与抑制Pink1的表达以及Mfn2和Parkin的磷酸化有关。总之，Notch1 发挥心肌保护作用，这与维持线粒体质量控制和抑制 Pink1/Mfn2/Parkin 信号传导有关。
Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad‐N1ICD and Ad‐shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.