A new alternative NF-κB pathway mediated the neuroprotection of GDNF on 6-OHDA-induced DA neurons neurotoxicity
| Autor: | Jing Chen, Meiying Liu, Yu Sun, Ting Wang, Hong-Jun Wang, Xiahong Xu, Honghua Yuan, Zhengquan Yu, Jing-Kao Yu, Hongyan Niu, Dianshuai Gao, Xiangui Huang, Junping Cao |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Active Transport Cell Nucleus IκB kinase Neuroprotection Cell Line Rats Sprague-Dawley Neurotrophic factors medicine Glial cell line-derived neurotrophic factor Animals Glial Cell Line-Derived Neurotrophic Factor Oxidopamine Molecular Biology biology General Neuroscience RELB Dopaminergic Neurons Neurotoxicity NF-kappa B medicine.disease Rats Neuroprotective Agents nervous system Cancer research biology.protein Neurology (clinical) Signal transduction GDNF family of ligands Developmental Biology Signal Transduction |
| Zdroj: | Brain research. 1437 |
| ISSN: | 1872-6240 |
| Popis: | Glial cell line-derived neurotrophic factor (GDNF) is a potent protective factor for dopaminergic (DA) neurons, but the signaling mechanisms underlying the effect of GDNF on these neurons remain obscure. Here, both our in vivo and in vitro studies demonstrate that the majority of DA neurons express the NF-κB-inducing kinase (NIK), which is the essential kinase for mediating activation of the new alternative NF-κB signaling pathway. Additionally, we also show that GDNF induced the time/dose-dependent phosphorylation of IκB kinase α (IKKα) and p100, facilitated the processing of p100 to p52 and accelerated the translocation of NF-κB dimmers into the nuclei of DA neurons. We furtherly found that the dimmer which translocate into the nucleus was RelA/p52 not RelB/p52. Meanwhile, the attenuation of 6-OHDA-induced DA neuronal apoptosis due to GDNF was reversed subsequent to the inhibition of p100 expression by RNAi while the neuroprotective effect of GDNF on injured DA neurons was strengthened by the overexpression of p100. Our data, therefore, indicate that a new alternative NF-κB signaling pathway, which was not the classic pathway but different from the non-canonical pathway, exists in DA neurons and mediates the neuroprotective effect of GDNF on these neurons. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect