The application of proteomics and phosphoproteomics to reveal the molecular mechanism of salidroside in ameliorating myocardial hypoxia
Zhongwei Xu,
Kaiyuan Fan,
Heng Li,
Lulu Wang,
Wenqing Zhu,
Shuang Zou,
Yan Zhang,
Yanan Liu,
Zhidong Wu,
Qian Gong,
Minjia Tan,
Jin Wang,
Linhui Zhai
Affiliations
Zhongwei Xu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Kaiyuan Fan
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China
Heng Li
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China; Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, 300170, China
Lulu Wang
State Key Laboratory of Pharmaceutical Research, Shanghai Institute of Materia Medica, CAS, Shanghai, 201203, China
Wenqing Zhu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Shuang Zou
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Yan Zhang
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Yanan Liu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Zhidong Wu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China
Qian Gong
Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, 300170, China
Minjia Tan
State Key Laboratory of Pharmaceutical Research, Shanghai Institute of Materia Medica, CAS, Shanghai, 201203, China
Jin Wang
Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, 300170, China; Corresponding author. Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, 300170, China.
Linhui Zhai
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; State Key Laboratory of Pharmaceutical Research, Shanghai Institute of Materia Medica, CAS, Shanghai, 201203, China; Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China; Corresponding author. State Key Laboratory of Pharmaceutical Research, Shanghai Institute of Materia Medica, CAS, Shanghai, 201203, China.
Salidroside (SAL), belonging to a kind of the main active ingredient of Rhodiola rosea, is extensively utilized for anti-hypoxia and prevention of altitude sickness in the plateau region of China. However, the research on the systemic changes induced by SAL at intracellular protein level is still limited, especially at protein phosphorylation level. These limitations hinder a comprehensive understanding of the regulatory mechanisms of SAL. This study aimed to investigate the potential molecular mechanism of SAL in ameliorating the acute myocardial hypoxia induced by cobalt chloride using integrated proteomics and phosphoproteomics. We successfully identified 165 differentially expressed proteins and 266 differentially expressed phosphosites in H9c2 cells following SAL treatment under hypoxic conditions. Bioinformatics analysis and biological experiment validation revealed that SAL significantly antagonized CoCl2-mediated cell cycle arrest by downregulating CCND1 expression and upregulating AURKA, AURKAB, CCND3 and PLK1 expression. Additionally, SAL can stabilize the cytoskeleton through upregulating the Kinesin Family (KIF) members expression. Our study systematically revealed that SAL had the ability to protect myocardial cells against CoCl2-induced hypoxia through multiple biological pathways, including enhancing the spindle stability, maintaining the cell cycle, relieving DNA damage, and antagonizing cell apoptosis. This study supplies a comprehension perspective on the alterations at protein and protein phosphorylation levels induced by SAL treatment, thereby expanded our knowledge of the anti-hypoxic mechanisms of SAL. Moreover, this study provides a valuable resource for further investigating the effects of SAL.
