20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4‑2 in kidney and liver through a neddylation modification pathway

  • Authors:
    • Jianzhu Zhao
    • Bijun Zhang
    • Guangrui Lai
    • Runhong Xu
    • Guoming Chu
    • Yanyan Zhao
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  • Published online on: October 17, 2017     https://doi.org/10.3892/mmr.2017.7803
  • Pages: 9671-9677
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Abstract

The present study aimed to test whether 20-hydroxyeicosatetraenoic acid (20‑HETE) affected neddylation modification of E3‑ligase Nedd4‑2 (neural precursor cell expressed, developmentally down‑regulated 4‑like, E3 ubiquitin protein ligase). A cytochrome P450 family 4 subfamily F member 2 (CYP4F2) transgenic mouse model that overproduces 20‑HETE in the kidney and the liver was used in the present study. Transgenic mice with high salt intake exhibited increased activation of Nedd4‑2‑mediated ubiquitin‑proteasome pathway. Nedd4‑2 expression is increased in the kidney and decreased in the liver of transgenic mice compared with wild‑type mice. Subsequently, co‑immunoprecipitation analysis indicated that Nedd4‑2 was modified by Nedd8, and the level of neddylation on Nedd4‑2 was reduced in the kidney and increased in the liver of transgenic mice compared with controls. In addition, sentrin‑specific protease 8 (Senp8), a deneddylation enzyme, is expressed higher in the kidney and lower in the liver of transgenic mice compared with wild‑type controls. The function of 20‑HETE on modulation of Nedd4‑2 were also confirmed in mouse M1 kidney and mouse NCTC1469 liver cell lines, and the function was restored by neddylation inhibitor MLN4924 Data from the present study demonstrated that 20‑HETE upregulated the expression of Nedd4‑2 in the kidney and downregulated expression in the liver through the neddylation modification pathway, at least partly, depending on the effects on Senp8 deneddylation.
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December-2017
Volume 16 Issue 6

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

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Spandidos Publications style
Zhao J, Zhang B, Lai G, Xu R, Chu G and Zhao Y: 20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4‑2 in kidney and liver through a neddylation modification pathway. Mol Med Rep 16: 9671-9677, 2017
APA
Zhao, J., Zhang, B., Lai, G., Xu, R., Chu, G., & Zhao, Y. (2017). 20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4‑2 in kidney and liver through a neddylation modification pathway. Molecular Medicine Reports, 16, 9671-9677. https://doi.org/10.3892/mmr.2017.7803
MLA
Zhao, J., Zhang, B., Lai, G., Xu, R., Chu, G., Zhao, Y."20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4‑2 in kidney and liver through a neddylation modification pathway". Molecular Medicine Reports 16.6 (2017): 9671-9677.
Chicago
Zhao, J., Zhang, B., Lai, G., Xu, R., Chu, G., Zhao, Y."20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4‑2 in kidney and liver through a neddylation modification pathway". Molecular Medicine Reports 16, no. 6 (2017): 9671-9677. https://doi.org/10.3892/mmr.2017.7803