Heliyon (May 2024)

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

Journal volume & issue
Vol. 10, no. 9
p. e30433

Abstract

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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.

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