Inhibition of CYP1B1 ameliorates cardiac hypertrophy induced by uremic toxin

  • Authors:
    • Ying Zhang
    • Shaobo Wang
    • Yinghui Huang
    • Ke Yang
    • Yong Liu
    • Xianjin Bi
    • Chi Liu
    • Jiachuan Xiong
    • Bo Zhang
    • Jinghong Zhao
    • Ling Nie
  • View Affiliations

  • Published online on: November 11, 2019     https://doi.org/10.3892/mmr.2019.10810
  • Pages: 393-404
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cardiovascular disease is the predominant complication and leading cause of mortality in patients with chronic kidney disease (CKD). Previous studies have revealed that uremic toxins, including indoxyl sulfate (IS), participate in cardiac hypertrophy. As a heme‑thiolate monooxygenase, cytochrome P450 family 1 subfamily B member 1 (CYP1B1) is able to metabolize arachidonic acid into hydroxyeicosatetraenoic acids, which are thought to serve a central function in the pathophysiology of the cardiovascular system. However, whether CYP1B1 is involved in cardiac hypertrophy induced by uremic toxins remains unknown. The present study revealed that the expression of the CYP1B1 gene was significantly (P<0.05, CKD or IS vs. control) upregulated by CKD serum or IS at the transcriptional and translational level. Furthermore, IS treatment resulted in the nuclear translocation of aryl hydrocarbon receptor (AhR), an endogenous ligand of IS. Binding of AhR in the promoter region of CYP1B1 was confirmed using a chromatin immunoprecipitation assay in the cardiomyoblast H9c2 cell line. In addition, knockdown of AhR or CYP1B1 reversed the production of cardiac hypertrophy markers. The in vivo injection of a CYP1B1 inhibitor significantly (P<0.05, Inhibitor vs. control) attenuated cardiac hypertrophy in mice. The data from the present study clearly demonstrated that CYP1B1 was involved in cardiac hypertrophy induced by uremic toxins.
View Figures
View References

Related Articles

Journal Cover

January-2020
Volume 21 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Wang S, Huang Y, Yang K, Liu Y, Bi X, Liu C, Xiong J, Zhang B, Zhao J, Zhao J, et al: Inhibition of CYP1B1 ameliorates cardiac hypertrophy induced by uremic toxin. Mol Med Rep 21: 393-404, 2020
APA
Zhang, Y., Wang, S., Huang, Y., Yang, K., Liu, Y., Bi, X. ... Nie, L. (2020). Inhibition of CYP1B1 ameliorates cardiac hypertrophy induced by uremic toxin. Molecular Medicine Reports, 21, 393-404. https://doi.org/10.3892/mmr.2019.10810
MLA
Zhang, Y., Wang, S., Huang, Y., Yang, K., Liu, Y., Bi, X., Liu, C., Xiong, J., Zhang, B., Zhao, J., Nie, L."Inhibition of CYP1B1 ameliorates cardiac hypertrophy induced by uremic toxin". Molecular Medicine Reports 21.1 (2020): 393-404.
Chicago
Zhang, Y., Wang, S., Huang, Y., Yang, K., Liu, Y., Bi, X., Liu, C., Xiong, J., Zhang, B., Zhao, J., Nie, L."Inhibition of CYP1B1 ameliorates cardiac hypertrophy induced by uremic toxin". Molecular Medicine Reports 21, no. 1 (2020): 393-404. https://doi.org/10.3892/mmr.2019.10810