Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage

  • Authors:
    • Tao Zuo
    • Jane Yuxia Qin
    • Jing Chen
    • Zixiao Shi
    • Meiying Liu
    • Xiuxian Gao
    • Dianshuai Gao
  • View Affiliations

  • Published online on: January 3, 2013     https://doi.org/10.3892/ijmm.2013.1226
  • Pages: 561-568
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Abstract

The aim of this study was to further confirm that glial cell line-derived neurotrophic factor (GDNF) exerts a neuro-protective effect on dopaminergic neurons (DAs) and to investigate the protective mechanism. Cadherins are calcium-dependent adhesion proteins, and N-cadherins are found in neurons. Our study attempted to ascertain whether GDNF activates the PI3K/Akt signaling pathway through the mediation of N-cadherin to confer a protective effect on DAs. Flow cytometry and Hoechst 33258 staining results indicated that the apoptosis rate of damaged neurocytes increased following interference of N-cadherin expression. Immunoblotting results demonstrated that the amount of phosphorylated Akt (p-Akt) in the cytoplasm decreased, while the total Akt quantity remained unchanged following interference of N-cadherin expression. The immunohistochemical staining results demonstrated that the levels of total N-cadherin, phosphorylated N-cadherin (Tyr860) and p-Akt decreased; however, the amount of total Akt remained unchanged. In addition, we also demonstrated that Tyr860 and p-Akt levels were reduced in a GDNF dose-dependent manner with the phosphorylation level peaking at GDNF dose of 50 ng/ml (in vitro) and 50 ng/4 µl (in vivo), and also in a time-dependent manner with the phosphorylation level peaking at 15 min (in vitro) and 30 min (in vivo). Statistical analysis also showed that changes in the phosphorylation levels of Tyr860 and p-Akt demonstrated a positive correlation. Collectively, GDNF activates the PI3K/Akt pathway via N-cadherin to protect DAs.
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March 2013
Volume 31 Issue 3

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

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Spandidos Publications style
Zuo T, Qin JY, Chen J, Shi Z, Liu M, Gao X and Gao D: Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage. Int J Mol Med 31: 561-568, 2013
APA
Zuo, T., Qin, J.Y., Chen, J., Shi, Z., Liu, M., Gao, X., & Gao, D. (2013). Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage. International Journal of Molecular Medicine, 31, 561-568. https://doi.org/10.3892/ijmm.2013.1226
MLA
Zuo, T., Qin, J. Y., Chen, J., Shi, Z., Liu, M., Gao, X., Gao, D."Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage". International Journal of Molecular Medicine 31.3 (2013): 561-568.
Chicago
Zuo, T., Qin, J. Y., Chen, J., Shi, Z., Liu, M., Gao, X., Gao, D."Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage". International Journal of Molecular Medicine 31, no. 3 (2013): 561-568. https://doi.org/10.3892/ijmm.2013.1226