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Volume 4 Issue 1
Jan.  2024
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Article Navigation >  Frigid Zone Medicine  > 2024  >  4(1): 51-64
Fangfang Bi, Miao Cao, Yuquan Wang, Qingming Pan, Zehong Jing, Danyang Bing, Lifang Lyu, Tong Yu, Tianyu Li, Xuelian Li, Haihai Liang, Hongli Shan, Yuhong Zhou. YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway[J]. Frigid Zone Medicine, 2024, 4(1): 51-64. doi: 10.2478/fzm-2024-0006
Citation: Fangfang Bi, Miao Cao, Yuquan Wang, Qingming Pan, Zehong Jing, Danyang Bing, Lifang Lyu, Tong Yu, Tianyu Li, Xuelian Li, Haihai Liang, Hongli Shan, Yuhong Zhou. YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway[J]. Frigid Zone Medicine, 2024, 4(1): 51-64. doi: 10.2478/fzm-2024-0006
shu

YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

doi: 10.2478/fzm-2024-0006
  • 1.

    Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China

  • 2.

    Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai 201620, China

  • 3.

    Department of Basic Medicine, Xiamen Medical College, Xiamen 361023, China

Funds:

Science and technology project of Xiamen Medical College K2023-08

the National Natural Science Foundation of China 82170299

the National Natural Science Foundation of China 82003757

More Information
  • Corresponding author: Hongli Shan, E-mail: shanhl@sues.edu.cn; Yuhong Zhou, E-mail: zyh2023@xmmc.edu.cn
  • Received Date: 2023-11-22
  • Accepted Date: 2024-01-22
    • Available Online: 2024-01-01
    Abstract
  •   Background  Myocardial infarction (MI) is associated with higher morbidity and mortality in the world, especially in cold weather. YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis. But YBX1, as an individual RNA-binding protein, regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.  Methods  In vivo, the mouse MI model was induced by ligating the left anterior descending coronary artery (LAD), and randomly divided into sham operation group, MI group, MI+ YBX1 knockdown/overexpression group and MI+ negative control (NC) group. The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining. In vitro, mitochondrial-dependent apoptosis was investigated by using CCK8, TUNEL staining, reactive oxygen species (ROS) staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes (NMCMs).  Results  YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition. Compared to mice induced by MI, YBX1 overexpression mediated by adeno-associated virus serotype 9 (AAV9) vector reduced the infarcted size and improved cardiac function. Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In hypoxic cardiomyocytes, YBX1 overexpression decreased lactic dehydrogenase (LDH) release, increased cell viability, and inhibited apoptosis by affecting the expression of apoptosis related proteins, while knockdown of endogenous YBX1 by siRNA had the opposite effect. Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS. In hypoxic NMCMs, YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase (PI3K)/AKT, and the antiapoptosis effect of YBX1 was eliminated t by LY294002, PI3K/AKT inhibitor.  Conclusion  YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway. It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

     

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