title: Involvement of N-cadherin in the protective effect of glial cell line-derived             neurotrophic factor on dopaminergic neuron damage.
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.
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Jiangsu, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.forename: Jane Yuxia
authors.initials: JY
authors.lastname: Qin
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Zixiao
authors.initials: Z
authors.lastname: Shi
authors.forename: Meiying
authors.initials: M
authors.lastname: Liu
authors.forename: Xiuxian
authors.initials: X
authors.lastname: Gao
authors.forename: Dianshuai
authors.initials: D
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D018696:Neuroprotective Agents; D010300:Parkinson Disease / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt