| First Author | He S | Year | 2020 |
| Journal | Oxid Med Cell Longev | Volume | 2020 |
| Pages | 7046923 | PubMed ID | 32724494 |
| Mgi Jnum | J:313538 | Mgi Id | MGI:6794892 |
| Doi | 10.1155/2020/7046923 | Citation | He S, et al. (2020) A Novel Molecular Mechanism of IKKepsilon-Mediated Akt/mTOR Inhibition in the Cardiomyocyte Autophagy after Myocardial Infarction. Oxid Med Cell Longev 2020:7046923 |
| abstractText | 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. IKKepsilon plays a crucial role in the occurrence of autophagy, but the functional role in MI remains largely unknown. To evaluate the impact of IKKepsilon on the autophagy of cardiomyocytes after MI, MI was induced by surgical left anterior descending coronary artery ligation in IKKepsilon knockout (KO) mice and wild-type (WT) mice. Starvation of H9c2 cells with IKKepsilon siRNA and rescued with IKKepsilon overexpressed afterwards to test the mechanism of IKKepsilon in autophagy in vitro. Our results demonstrated that the expression of IKKepsilon was upregulated in mice myocardial tissues which were consistent with cardiomyocyte autophagy after MI. Significantly, the IKKepsilon 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 IKKepsilon induces excessive cardiomyocyte autophagy and reduced the expression of p-Akt and p-mTOR. Similar results were observed in IKKepsilon siRNA H9c2 cells in vitro which were under starvation injury. Notably, the levels of p-Akt and p-mTOR can restore in IKKepsilon rescued cells. In conclusion, our results indicated that IKKepsilon protects cardiomyocyte survival by reduced autophagy following MI via regulation of the Akt/mTOR signaling pathway. Thus, our study suggests that IKKepsilon might represent a potential therapeutic target for the treatment of MI. |
