Abstract |
In this study, we studied the effect of glycogen synthase kinase-3 (GSK-3) overactivation on neurofilament phosphorylation in cultured cells. After N2a cells were treated with the specific inhibitor ( wortmannin) of phosphoinositol-3 kinase (PI-3K) or treated with wortmannin and the specific inhibitor (LiCl) of glycogen synthase kinase-3 (GSK-3), GSK-3 activity and neurofilament phosphorylation were detected by using GSK-3 activity assay, Western blots and immunofluoresence. Our results showed that after treatment of N2a cells with wortmannin for 1 h, overactivation of GSK-3 caused a reduced staining with antibody SMI32 and an enhanced staining with antibody SMI31. When N2a cells were treated with wortmannin and LiCl, the activity of GSK-3 was reduced substantially. At the same time, the phosphorylation of neurofilament was also reduced. The study demonstrated that overactivation of GSK-3 induced hyperphosphorylation of neurofilament and suggested that in vitro overactivation of GSK-3 resulted in neurofilament hyperphosphorylation and this may be the underlying mechanism for Alzheimer's disease.
|
Authors | Juan Chen, Jie Zhou, Youmei Feng, Jianzhi Wang |
Journal | Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban
(J Huazhong Univ Sci Technolog Med Sci)
Vol. 25
Issue 4
Pg. 375-7, 403
( 2005)
ISSN: 1672-0733 [Print] China |
PMID | 16196280
(Publication Type: Journal Article)
|
Chemical References |
- Androstadienes
- Neurofilament Proteins
- Phosphoinositide-3 Kinase Inhibitors
- Glycogen Synthase Kinase 3
- Wortmannin
|
Topics |
- Alzheimer Disease
(pathology)
- Androstadienes
(pharmacology)
- Animals
- Glycogen Synthase Kinase 3
(antagonists & inhibitors, metabolism)
- Mice
- Neuroblastoma
(enzymology, pathology)
- Neurofilament Proteins
(metabolism)
- Phosphoinositide-3 Kinase Inhibitors
- Phosphorylation
- Tumor Cells, Cultured
- Wortmannin
|