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Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells

  • Authors:
    • Seong Kwon Ma
    • Soo Yeon Joo
    • Hoon-In Choi
    • Eun Hui Bae
    • Kwang Il Nam
    • Jongun Lee
    • Soo Wan Kim

  • View Affiliations

  • Published online on: August 1, 2014     https://doi.org/10.3892/ijmm.2014.1874
  • Pages: 1117-1123
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Abstract

G-protein-coupled receptor 40 (GPR40) is known to play a role in the regulation of fatty acids, insulin secretion and inflammation. However, the pathophysiological roles of GPR40 in kidney disease have not yet been identified. In the present study, we investigated the expression of GPR40 during cisplatin-induced kidney injury using male Sprague-Dawley rats that were treated with 8 mg/kg cisplatin. Control rats were treated with saline. Following treatment with cisplatin, the protein expression of GPR40 in the kidneys was decreased in association with an increase in serum creatinine levels and the Bax/Bcl-2 expression ratio. To further investigate the function of GPR40, the human renal proximal tubule epithelial cell line (HK-2) was cultured with cisplatin in the absence or presence of GW9508, a selective GPR40 agonist. Pre-treatment of the HK-2 cells with GW9508 attenuated the decrease in cell viability induced by treatment with cisplatin. Treatment with cisplatin increased the number of cells with condensed nuclei, which was ameliorated by GW9508 pre-treatment. TUNEL assay also revealed that pre-treatment with GW9508 ameliorated cisplatin-induced apoptosis. Treatment with cisplatin increased the Bax/Bcl-2 expression ratio and cleaved caspase-3 expression, and promoted the activation of nuclear factor-κB (NF-κB). These changes were attenuated by pre-treatment with GW9508. The cisplatin-induced generation of reactive oxygen species (ROS) and the activation of the Src/epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway were also counteracted by pre-treatment with GW9508. Thus, the activation of GPR40 attenuates cisplatin-induced apoptosis by inhibiting the generation of ROS, the activation of the Src/EGFR/ERK signaling pathway and the nuclear activation of NF-κB and pro-apoptotic factors.
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October 2014
Volume 34 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Journal Metrics
  • Impact Factor: 5.7
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 12.3
  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
Ma SK, Joo SY, Choi H, Bae EH, Nam KI, Lee J and Kim SW: Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells. Int J Mol Med 34: 1117-1123, 2014.
APA
Ma, S.K., Joo, S.Y., Choi, H., Bae, E.H., Nam, K.I., Lee, J., & Kim, S.W. (2014). Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells. International Journal of Molecular Medicine, 34, 1117-1123. https://doi.org/10.3892/ijmm.2014.1874
MLA
Ma, S. K., Joo, S. Y., Choi, H., Bae, E. H., Nam, K. I., Lee, J., Kim, S. W."Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells". International Journal of Molecular Medicine 34.4 (2014): 1117-1123.
Chicago
Ma, S. K., Joo, S. Y., Choi, H., Bae, E. H., Nam, K. I., Lee, J., Kim, S. W."Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells". International Journal of Molecular Medicine 34, no. 4 (2014): 1117-1123. https://doi.org/10.3892/ijmm.2014.1874