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22-09-2023 | Myocardial Infarction

Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway

Authors: Yuyang Yang, Fangqian Liang, Jingyuan Gao, Jian Li, Chunhua Jiang, Wei Xie, Shujuan Wu, Ya Wang, Jing Yi

Published in: Cardiovascular Toxicology | Issue 11-12/2023

Abstract

Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ_0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1β, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ_0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ_0097682 expression. In addition, circ_0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ_0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ_0097682/miR-671-5p/USP46 pathway.

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White, H. D., Thygesen, K., Alpert, J. S., & Jaffe, A. S. (2014). Clinical implications of the third universal definition of myocardial infarction. Heart, 100, 424–432.CrossRefPubMed

Wang, Z. Y., Liu, X. X., & Deng, Y. F. (2022). Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction. Cell Death and Differentiation, 29, 709–721.CrossRefPubMed

Yang, H. T., Xiu, W. J., Zheng, Y. Y., Liu, F., Gao, Y., Ma, X., et al. (2019). Invasive reperfusion after 12 hours of the symptom onset remains beneficial in patients with ST-segment elevation myocardial infarction: Evidence from a meta-analysis of published data. Cardiology Journal, 26, 333–342.CrossRefPubMedPubMedCentral

Chen, P., Liu, J., Ruan, H., Zhang, M., Wu, P., Yimei, D., et al. (2019). Protective effects of Salidroside on cardiac function in mice with myocardial infarction. Science and Reports, 9, 18127.CrossRef

Yu, S., Liu, M., Gu, X., & Ding, F. (2008). Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. Cellular and Molecular Neurobiology, 28, 1067–1078.CrossRefPubMed

Wang, H., Ding, Y., Zhou, J., Sun, X., & Wang, S. (2009). The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3. Phytomedicine, 16, 146–155.CrossRefPubMed

Wu, Y. L., Piao, D. M., Han, X. H., & Nan, J. X. (2008). Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biological and Pharmaceutical Bulletin, 31, 1523–1529.CrossRefPubMed

Guan, S., Feng, H., Song, B., Guo, W., Xiong, Y., Huang, G., et al. (2011). Salidroside attenuates LPS-induced pro-inflammatory cytokine responses and improves survival in murine endotoxemia. International Immunopharmacology, 11, 2194–2199.CrossRefPubMed

Ming, D. S., Hillhouse, B. J., Guns, E. S., Eberding, A., Xie, S., Vimalanathan, S., et al. (2005). Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytotherapy Research, 19, 740–743.CrossRefPubMed

10.

Zhong, H., Xin, H., Wu, L. X., & Zhu, Y. Z. (2010). Salidroside attenuates apoptosis in ischemic cardiomyocytes: A mechanism through a mitochondria-dependent pathway. Journal of Pharmacological Sciences, 114, 399–408.CrossRefPubMed

11.

Yu, C. Y., & Kuo, H. C. (2019). The emerging roles and functions of circular RNAs and their generation. Journal of Biomedical Science, 26, 29.CrossRefPubMedPubMedCentral

12.

Zhu, G., Chang, X., Kang, Y., Zhao, X., Tang, X., Ma, C., et al. (2012). CircRNA: A novel potential strategy to treat thyroid cancer (Review). International Journal of Molecular Medicine. https://doi.org/10.3892/ijmm.2021.5034CrossRefPubMedPubMedCentral

13.

Zhang, F., Zhang, R., Zhang, X., Wu, Y., Li, X., Zhang, S., et al. (2018). Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits. Aging (Albany NY)., 10, 2266–2283.CrossRefPubMedPubMedCentral

14.

Altesha, M. A., Ni, T., Khan, A., Liu, K., & Zheng, X. (2019). Circular RNA in cardiovascular disease. Journal of Cellular Physiology, 234, 5588–5600.CrossRefPubMed

15.

Zheng, H., Huang, S., Wei, G., Sun, Y., Li, C., Si, X., et al. (2022). CircRNA Samd4 induces cardiac repair after myocardial infarction by blocking mitochondria-derived ROS output. Molecular Therapy, 30, 3477–3498.CrossRefPubMed

16.

Liu, X., Wang, M., Li, Q., Liu, W., Song, Q., & Jiang, H. (2022). CircRNA ACAP2 induces myocardial apoptosis after myocardial infarction by sponging miR-29. Minerva Medica, 113, 128–134.CrossRefPubMed

17.

Jin, P., Li, L. H., Shi, Y., & Hu, N. B. (2021). Salidroside inhibits apoptosis and autophagy of cardiomyocyte by regulation of circular RNA hsa_circ_0000064 in cardiac ischemia-reperfusion injury. Gene, 767, 145075.CrossRefPubMed

18.

Yin, L., Tang, Y., & Jiang, M. (2021). Research on the circular RNA bioinformatics in patients with acute myocardial infarction. Journal of Clinical Laboratory Analysis, 35, e23621.CrossRefPubMed

19.

Correia, C., Koshkin, A., Carido, M., Espinha, N., Šarić, T., Lima, P. A., et al. (2016). Effective hypothermic storage of human pluripotent stem cell-derived cardiomyocytes compatible with global distribution of cells for clinical applications and toxicology testing. Stem Cells Translational Medicine, 5, 658–669.CrossRefPubMedPubMedCentral

20.

Correia, C., Koshkin, A., Duarte, P., Hu, D., Carido, M., Sebastião, M. J., et al. (2018). 3D aggregate culture improves metabolic maturation of human pluripotent stem cell derived cardiomyocytes. Biotechnology and Bioengineering., 115, 630–644.CrossRefPubMed

21.

Wang, X., Ren, L., Chen, S., Tao, Y., Zhao, D., & Wu, C. (2022). Long non-coding RNA MIR4435-2HG/microRNA-125a-5p axis is involved in myocardial ischemic injuries. Bioengineered, 13, 10707–10720.CrossRefPubMedPubMedCentral

22.

Sebastião, M. J., Serra, M., Pereira, R., Palacios, I., Gomes-Alves, P., & Alves, P. M. (2019). Human cardiac progenitor cell activation and regeneration mechanisms: Exploring a novel myocardial ischemia/reperfusion in vitro model. Stem Cell Research & Therapy, 10, 77.CrossRef

23.

Sun, D., Chen, L., Lv, H., Gao, Y., Liu, X., & Zhang, X. (2020). Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940. Oncotargets and Therapy, 13, 1569–1581.CrossRefPubMedPubMedCentral

24.

Zhuang, W., Yue, L., Dang, X., Chen, F., Gong, Y., Lin, X., et al. (2019). Rosenroot (Rhodiola): Potential applications in aging-related diseases. Aging & Disease, 10, 134–146.CrossRef

25.

Kong, Y. H., & Xu, S. P. (2018). Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis. Oncology Reports, 39, 2513–2526.PubMedPubMedCentral

26.

Xu, N., Huang, F., Jian, C., Qin, L., Lu, F., Wang, Y., et al. (2019). Neuroprotective effect of salidroside against central nervous system inflammation-induced cognitive deficits: A pivotal role of sirtuin 1-dependent Nrf-2/HO-1/NF-κB pathway. Phytotherapy Research, 33, 1438–1447.CrossRefPubMed

27.

Qi, Z., Qi, S., Ling, L., Lv, J., & Feng, Z. (2016). Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus. International Immunopharmacology, 35, 265–271.CrossRefPubMed

28.

Zhao, D., Sun, X., Lv, S., Sun, M., Guo, H., Zhai, Y., et al. (2019). Salidroside attenuates oxidized low-density lipoprotein-induced endothelial cell injury via promotion of the AMPK/SIRT1 pathway. International Journal of Molecular Medicine, 43, 2279–2290.PubMedPubMedCentral

29.

Zhang, L., Zhang, Y., Yu, F., Li, X., Gao, H., & Li, P. (2022). The circRNA-miRNA/RBP regulatory network in myocardial infarction. Frontiers in Pharmacology, 13, 941123.CrossRefPubMedPubMedCentral

30.

Wen, Z. J., Xin, H., Wang, Y. C., Liu, H. W., Gao, Y. Y., & Zhang, Y. F. (2021). Emerging roles of circRNAs in the pathological process of myocardial infarction. Mol Ther Nucleic Acids., 26, 828–848.CrossRefPubMedPubMedCentral

31.

Boon, R., & Dimmeler, S. (2015). MicroRNAs in myocardial infarction. Nature reviews Cardiology, 12, 135–142.CrossRefPubMed

32.

Fiedler, J., & Thum, T. (2013). MicroRNAs in myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology., 33, 201–205.CrossRefPubMed

33.

Ghafouri-Fard, S., Askari, A., Hussen, B. M., Rasul, M. F., Hatamian, S., Taheri, M., et al. (2022). A review on the role of miR-671 in human disorders. Frontiers in Molecular Biosciences, 9, 1077968.CrossRefPubMedPubMedCentral

34.

Wang, X., Zhu, Y., Wu, C., Liu, W., He, Y., & Yang, Q. (2021). Adipose-derived mesenchymal stem cells-derived exosomes carry MicroRNA-671 to alleviate myocardial infarction through inactivating the TGFBR2/Smad2 Axis. Inflammation, 44, 1815–1830.CrossRefPubMed

35.

Walsh, C. T., Garneau-Tsodikova, S., & Gatto, G. J., Jr. (2005). Protein posttranslational modifications: The chemistry of proteome diversifications. Angewandte Chemie (International ed. in English), 44, 7342–7372.CrossRefPubMed

36.

Imai, S., Kano, M., Nonoyama, K., & Ebihara, S. (2013). Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice. PLoS ONE, 8, e58566.CrossRefPubMedPubMedCentral

37.

Nijman, S. M., Luna-Vargas, M. P., Velds, A., Brummelkamp, T. R., Dirac, A. M., Sixma, T. K., et al. (2005). A genomic and functional inventory of deubiquitinating enzymes. Cell, 123, 773–786.CrossRefPubMed

38.

Ye, X., Hang, Y., Lu, Y., Li, D., Shen, F., Guan, P., et al. (2021). CircRNA circ-NNT mediates myocardial ischemia/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression. Cell Death Discov., 7, 370.CrossRefPubMedPubMedCentral

Title: Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway
Authors: Yuyang Yang
Fangqian Liang
Jingyuan Gao
Jian Li
Chunhua Jiang
Wei Xie
Shujuan Wu
Ya Wang
Jing Yi
Publication date: 22-09-2023
Publisher: Springer US
Keyword: Myocardial Infarction
Published in: Cardiovascular Toxicology / Issue 11-12/2023
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-023-09808-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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