The involvement of NF-kappaB p65/p52 in the effects of GDNF on DA neurons in early PD rats.
Glial cell line-derived neurotrophic factor (GDNF) can exert neuroprotective effects on the substantia nigra pars compacta (SNc) dopaminergic (DA) neurons that are undergoing degeneration in Parkinson's disease (PD). In an attempt to investigate the molecular signaling mechanisms underlying GDNF protection the DA neurons from degeneration, we established early PD rat models in which the DA neurons in SNc were degenerating. Whether the cytoplasmic NF-kappaB signaling pathway was involved in the protection of GDNF on the degenerating DA neurons was examined in the present study. The results showed that the nuclear NF-kappaB p65 levels in the DA neurons increased when GDNF was injected into SNc of early PD rat models. Immunoprecipitation assays showed that the nuclear NF-kappaB p65/p52 complex levels increased after GDNF administration, while the p65/p50 complex levels decreased. These results indicated that GDNF could activate the NF-kappaB signaling pathway in the degenerating DA neurons. And it was the noncanonical NF-kappaB signaling pathway, which contained the NF-kappaB p65/p52 complex that was involved in the effects of GDNF on DA neurons.
Department of Neurobiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu 221002, PR China. junping3177@sina.com
Jun Ping
JP
Cao
Hong Jun
HJ
Wang
Jing Kao
JK
Yu
Hong Mei
HM
Liu
Dian Shuai
DS
Gao
D018663:Adrenergic Agents / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016627:Oxidopamine / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D052003:NF-kappa B p52 Subunit; D051996:Transcription Factor RelA; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine