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Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress

  • Authors:
    • Shasha Yu
    • Hongmei Yang
    • Xiaofan Guo
    • Yingxian Sun
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 66
    |
    Published online on: November 19, 2020
       https://doi.org/10.3892/mmr.2020.11705
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Abstract

Hyperglycemia is known to lead to cardiac injury and inflammation through the reactive oxygen species (ROS)‑Toll‑like receptor 4 (TLR4)‑necroptosis pathway. Similarly, angiotensin II (Ang II) activates the TLR4‑nuclear factor κB (NF‑κB) p65 pathway, while the protein Klotho is known to inhibit this pathway, protecting cardiac cells from Ang II‑induced injury. However, there is currently a lack of data on whether necroptosis participates in Ang II‑induced cardiac injury and whether the Klotho protein has an effect on this process. The present study aimed to explore whether inhibition of the TLR4/NF‑κB p65 necroptosis pathway is involved in the Klotho protein‑mediated protection against the Ang II‑induced cardiac injury and inflammation. H9c2 cardiac cells were incubated with 0.01 mM Ang II. Western blotting was used to assess the expression of receptor‑interacting protein kinase 3 (RIP3), mixed‑lineage kinase domain‑like protein (MLKL), TLR4 and NF‑κB p65. The present study also assessed injury indexes: Inflammatory cytokine expression, mitochondrial membrane potential (ΔΨm), apoptosis, ROS production and cell viability. The expression of TLR4, phosphorylated (p)‑NF‑κB p65, RIP3 and MLKL were increased by incubation with Ang II in H9c2 cells. The pretreatment of H9c2 cells with necrostatin‑1 (Nec‑1, an inhibitor of necroptosis) or TAK‑242 (a small molecule inhibitor of TLR4) attenuated the upregulation of RIP3 and MLKL caused by Ang II. Klotho protein cotreatment also reversed the Ang II‑induced upregulation of TLR4, p‑NF‑κB p65, RIP3 and MLKL. Furthermore, Ang II decreased cell viability and upregulated the secretion of inflammatory cytokines, ΔΨm loss and ROS generation blocked by pretreatment with Nec‑1 or Klotho protein. Thus, it was determined that Klotho can attenuate the Ang II‑induced necroptosis of cardiomyocytes through the TLR4/NF‑κB p65 pathway, which suggests that Klotho could be a potential therapeutic drug against Ang II‑induced cardiotoxicity.
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1 

Adameova A, Goncalvesova E, Szobi A and Dhalla NS: Necroptotic cell death in failing heart: Relevance and proposed mechanisms. Heart Fail Rev. 21:213–221. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Zhu H and Sun A: Programmed necrosis in heart disease: Molecular mechanisms and clinical implications. J Mol Cell Cardiol. 116:125–134. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Guo X, Yin H, Li L, Chen Y, Li J, Doan J, Steinmetz R and Liu Q: Cardioprotective role of tumor necrosis factor receptor-associated factor 2 by suppressing apoptosis and necroptosis. Circulation. 136:729–742. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Mencke R and Hillebrands JL; NIGRAM consortium, : The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology. Ageing Res Rev. 35:124–146. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Kuro-O M: The Klotho proteins in health and disease. Nat Rev Nephrol. 15:27–44. 2019. View Article : Google Scholar : PubMed/NCBI

6 

Guo Y, Zhuang X, Huang Z, Zou J, Yang D, Hu X, Du Z, Wang L and Liao X: Klotho protects the heart from hyperglycemia-induced injury by inactivating ROS and NF-κB-mediated inflammation both in vitro and in vivo. Biochim Biophys Acta Mol Basis Dis. 1864:238–251. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Qian Y, Guo X, Che L, Guan X, Wu B, Lu R, Zhu M, Pang H, Yan Y, Ni Z and Gu L: Klotho reduces necroptosis by targeting oxidative stress involved in renal ischemic-reperfusion injury. Cell Physiol Biochem. 45:2268–2282. 2018. View Article : Google Scholar : PubMed/NCBI

8 

Chen Y, Yu S, Zhang N, Li Y, Chen S, Chang Y, Sun G and Sun Y: Atorvastatin prevents angiotensin II induced myocardial hypertrophy in vitro via CCAAT/enhancer-binding protein β. Biochem Biophys Res Commun. 486:423–430. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Zavodszky E, Seaman MN, Moreau K, Jimenez-Sanchez M, Breusegem SY, Harbour ME and Rubinsztein DC: Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun. 5:38282014. View Article : Google Scholar : PubMed/NCBI

10 

Lin M, Yiu WH, Wu HJ, Chan LY, Leung JC, Au WS, Chan KW, Lai KN and Tang SC: Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy. J Am Soc Nephrol. 23:86–102. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Qin S, Yang C, Huang W, Du S, Mai H, Xiao J and Lü T: Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia. Pharmacol Res. 133:218–235. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Szobi A, Goncalvesova E, Varga ZV, Leszek P, Kuśmierczyk M, Hulman M, Kyselovič J, Ferdinandy P and Adameová A: Analysis of necroptotic proteins in failing human hearts. J Transl Med. 15:862017. View Article : Google Scholar : PubMed/NCBI

13 

Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, Liu Y, Zheng W, Shang H, Zhang J, et al: CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med. 22:175–182. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Li L, Chen Y, Doan J, Murray J, Molkentin JD and Liu Q: Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling. Circulation. 130:2162–2172. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Oerlemans MI, Liu J, Arslan F, den Ouden K, van Middelaar BJ, Doevendans PA and Sluijter JPG: Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res Cardiol. 107:2702012. View Article : Google Scholar : PubMed/NCBI

16 

Zhang DY, Wang BJ, Ma M, Yu K, Zhang Q and Zhang XW: MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice. BMC Mol Biol. 20:172019. View Article : Google Scholar : PubMed/NCBI

17 

Zhao M, Qin Y, Lu L, Tang X, Wu W, Fu H and Liu X: Preliminary study of necroptosis in cardiac hypertrophy induced by pressure overload. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 32:618–623. 2015.(In Chinese). PubMed/NCBI

18 

Wu C, Lv C, Chen F, Ma X, Shao Y and Wang Q: The function of miR-199a-5p/Klotho regulating TLR4/NF-κB p65/NGAL pathways in rat mesangial cells cultured with high glucose and the mechanism. Mol Cell Endocrinol. 417:84–93. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Jin M, Lv P, Chen G, Wang P, Zuo Z, Ren L, Bi J, Yang CW, Mei X and Han D: Klotho ameliorates cyclosporine A-induced nephropathy via PDLIM2/NF-kB p65 signaling pathway. Biochem Biophys Res Commun. 486:451–457. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu S, Yang H, Guo X and Sun Y: Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress. Mol Med Rep 23: 66, 2021.
APA
Yu, S., Yang, H., Guo, X., & Sun, Y. (2021). Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress. Molecular Medicine Reports, 23, 66. https://doi.org/10.3892/mmr.2020.11705
MLA
Yu, S., Yang, H., Guo, X., Sun, Y."Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress". Molecular Medicine Reports 23.1 (2021): 66.
Chicago
Yu, S., Yang, H., Guo, X., Sun, Y."Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress". Molecular Medicine Reports 23, no. 1 (2021): 66. https://doi.org/10.3892/mmr.2020.11705
Copy and paste a formatted citation
x
Spandidos Publications style
Yu S, Yang H, Guo X and Sun Y: Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress. Mol Med Rep 23: 66, 2021.
APA
Yu, S., Yang, H., Guo, X., & Sun, Y. (2021). Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress. Molecular Medicine Reports, 23, 66. https://doi.org/10.3892/mmr.2020.11705
MLA
Yu, S., Yang, H., Guo, X., Sun, Y."Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress". Molecular Medicine Reports 23.1 (2021): 66.
Chicago
Yu, S., Yang, H., Guo, X., Sun, Y."Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress". Molecular Medicine Reports 23, no. 1 (2021): 66. https://doi.org/10.3892/mmr.2020.11705
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