1. Deptor protects against myocardial ischemia-reperfusion injury by regulating the mTOR signaling and autophagy
- Author
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Qunjun Duan, Weijun Yang, Xian Zhu, Zhanzeng Feng, Jiangwei Song, Xiaobin Xu, Minjian Kong, Jiayan Mao, Jian Shen, Yuqin Deng, Rujia Tao, Hongfei Xu, Wei Chen, Weidong Li, Aiqiang Dong, and Jie Han
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Deptor knockout mice were constructed by crossing Deptor Floxp3 mice with myh6 Cre mice, establishing a myocardial ischemia-reperfusion (I/R) model. Deptor knockout mice exhibited significantly increased myocardial infarction size and increased myocardial apoptosis in vivo. ELISA analysis indicated that the expression of CK-MB, LDH, and CtnT/I was significantly higher in the Deptor knockout mice. Deptor siRNA significantly reduced cell activity and increased myocardial apoptosis after I/R-induced in vitro. Deptor siRNA also significantly up-regulated the expression of p-mTOR, p-4EBP1, and p62, and down-regulated the expression of LC3 after I/R induction. Immunofluorescence indicated that LC3 dual fluorescence was weakened by Deptor knockout, and was enhanced after transfection with Deptor-overexpression plasmids. Treatment with OSI027, a co-inhibitor of mTORC1 and mTORC2, in either Deptor knockout mice or Deptor knockout H9C2 cells, resulted in a significant reduction in infarction size and apoptotic cardiomyocytes. ELISA analysis also showed that the expression of CK-MB, LDH, and CtnT/I were significantly down-regulated by treatment with OSI027. CCK-8 cell viability indicated that cell viability was enhanced, and the number of apoptotic cells was decreased in vitro following treatment with OSI027. These results revealed that OSI027 exerts a protective effect on myocardial ischemia/reperfusion injury in both an in vivo and in an in vitro model of I/R. These findings demonstrate that Deptor protects against I/R-induced myocardial injury by inhibiting the mTOR pathway and by increasing autophagy.
- Published
- 2024
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