A Novel Molecular Mechanism of IKKε-Mediated Akt/mTOR Inhibition in the Cardiomyocyte Autophagy after Myocardial Infarction. (17th July 2020)

• Record Type: Journal Article
• Authors: He, Shuai; Shen, Jian; Li, Liangpeng; Xu, Yueyue; Cao, Yide; Yin, Li; Tao, Zhonghao; Qiu, Zhibing; Chen, Wen; Chen, Xin
• Other Names: Altieri Fabio Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2020(2020)
• Publication Date: 2020-07-17
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2020/7046923
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Autophagy of cardiomyocytes after myocardial infarction (MI) is an important factor affecting the prognosis of MI. Excessive autophagy can lead to massive death of cardiomyocytes, which will seriously affect cardiac function. IKK ε plays a crucial role in the occurrence of autophagy, but the functional role in MI remains largely unknown. To evaluate the impact of IKK ε on the autophagy of cardiomyocytes after MI, MI was induced by surgical left anterior descending coronary artery ligation in IKK ε knockout (KO) mice and wild-type (WT) mice. Starvation of H9c2 cells with IKK ε siRNA and rescued with IKK ε overexpressed afterwards to test the mechanism of IKK ε in autophagy in vitro . Our results demonstrated that the expression of IKK ε was upregulated in mice myocardial tissues which were consistent with cardiomyocyte autophagy after MI. Significantly, the IKK ε KO mice showed increased infarct size, decreased viable cardiomyocytes, and exacerbated cardiac dysfunction when compared with the wild-type mice. Western blot and electron micrography analysis also revealed that loss of IKK ε induces excessive cardiomyocyte autophagy and reduced the expression of p-Akt and p-mTOR. Similar results were observed in IKK ε siRNA H9c2 cells in vitro which were under starvation injury. Notably, the levels of p-Akt and p-mTOR can restore in IKK ε rescued cells. In conclusion, our results indicated that IKK ε protects cardiomyocyte survival by reduced autophagy following MI via regulation of the Akt/mTOR signaling pathway. Thus, our study suggests that IKK ε might represent a potential therapeutic target for the treatment of MI.