Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
October 2014 Volume 34 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October 2014 Volume 34 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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 / Copyright

    Affiliations: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea, Department of Anatomy, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea, Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea
  • Pages: 1117-1123
    |
    Published online on: August 1, 2014
       https://doi.org/10.3892/ijmm.2014.1874
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Yao X, Panichpisal K, Kurtzman N and Nugent K: Cisplatin nephrotoxicity: a review. Am J Med Sci. 334:115–124. 2007. View Article : Google Scholar

2 

Pabla N and Dong Z: Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 73:994–1007. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Arany I, Megyesi JK, Kaneto H, Price PM and Safirstein RL: Cisplatin-induced cell death is EGFR/src/ERK signaling dependent in mouse proximal tubule cells. Am J Physiol Renal Physiol. 287:F543–F549. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Jo SK, Cho WY, Sung SA, Kim HK and Won NH: MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis. Kidney Int. 67:458–466. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Kim YK, Kim HJ, Kwon CH, Kim JH, Woo JS, Jung JS and Kim JM: Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol. 25:374–382. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Mishima K, Baba A, Matsuo M, Itoh Y and Oishi R: Protective effect of cyclic AMP against cisplatin-induced nephrotoxicity. Free Radic Biol Med. 40:1564–1577. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Li S, Gokden N, Okusa MD, Bhatt R and Portilla D: Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF. Am J Physiol Renal Physiol. 289:F469–F480. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Lee S, Kim W, Moon SO, et al: Rosiglitazone ameliorates cisplatin-induced renal injury in mice. Nephrol Dial Transplant. 21:2096–2105. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Sung MJ, Kim DH, Jung YJ, et al: Genistein protects the kidney from cisplatin-induced injury. Kidney Int. 74:1538–1547. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Sum CS, Tikhonova IG, Neumann S, Engel S, Raaka BM, Costanzi S and Gershengorn MC: Identification of residues important for agonist recognition and activation in GPR40. J Biol Chem. 282:29248–29255. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Itoh Y, Kawamata Y, Harada M, et al: Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 422:173–176. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Bharate SB, Nemmani KV and Vishwakarma RA: Progress in the discovery and development of small-molecule modulators of G-protein-coupled receptor 40 (GPR40/FFA1/FFAR1): an emerging target for type 2 diabetes. Expert Opin Ther Pat. 19:237–264. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Gowda N, Dandu A, Singh J, et al: Treatment with CNX-011-67, a novel GPR40 agonist, delays onset and progression of diabetes and improves beta cell preservation and function in male ZDF rats. BMC Pharmacol Toxicol. 14:282013. View Article : Google Scholar : PubMed/NCBI

14 

Wagner R, Kaiser G, Gerst F, et al: Reevaluation of fatty acid receptor 1 as a drug target for the stimulation of insulin secretion in humans. Diabetes. 62:2106–2111. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T and Narumiya S: A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol. 131:1660–1667. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Wauquier F, Philippe C, Léotoing L, et al: The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem. 288:6542–6551. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Kim SW, Lee JU, Nah MY, Kang DG, Ahn KY, Lee HS and Choi KC: Cisplatin decreases the abundance of aquaporin water channels in rat kidney. J Am Soc Nephrol. 12:875–882. 2001.PubMed/NCBI

18 

Ma SK, Choi JS, Joo SY, et al: Activation of the renal PI3K/Akt/mTOR signaling pathway in a DOCA-salt model of hypertension. Chonnam Med J. 48:150–154. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Rosenau C, Emery D, Kaboord B and Qoronfleh MW: Development of a high-throughput plate-based chemiluminescent transcription factor assay. J Biomol Screen. 9:334–342. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Bae EH, Lee J, Ma SK, et al: alpha-Lipoic acid prevents cisplatin-induced acute kidney injury in rats. Nephrol Dial Transplant. 24:2692–2700. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Park JW, Cho JW, Joo SY, et al: Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation. Eur J Pharmacol. 683:301–309. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Briscoe CP, Tadayyon M, Andrews JL, et al: The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem. 278:11303–11311. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Lee S, Moon SO, Kim W, et al: Protective role of L-2-oxothiazolidine-4-carboxylic acid in cisplatin-induced renal injury. Nephrol Dial Transplant. 21:2085–2095. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Mukhopadhyay P, Horváth B, Zsengellér Z, et al: Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy. Free Radic Biol Med. 52:497–506. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Chen J, Chen JK, Nagai K, et al: EGFR signaling promotes TGFβ-dependent renal fibrosis. J Am Soc Nephrol. 23:215–224. 2012.

26 

Chen J, Chen JK and Harris RC: Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway. Mol Cell Biol. 32:981–991. 2012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team