共 27 条
Cleavage of the cyclin-dependent kinase 5 activator p35 to p25 does not induce tau hyperphosphorylation
被引:37
作者:

Kerokoski, P
论文数: 0 引用数: 0
h-index: 0
机构: Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland

Suuronen, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland

Salminen, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland

Soininen, H
论文数: 0 引用数: 0
h-index: 0
机构: Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland

Pirttilä, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland
机构:
[1] Univ Kuopio, Dept Neurosci & Neurol, Kuopio 70211, Finland
[2] Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland
基金:
芬兰科学院;
关键词:
Alzheimer's disease;
cell death;
calpain;
glutamate;
NMDA;
lonomycin;
A23187;
MDL28170;
D O I:
10.1016/S0006-291X(02)02543-3
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Hyperphosphorylated tau protein is the primary component of neurofibrillary tangles observed in several neurodegenerative disorders. It has been hypothesized that in certain pathological conditions, the calcium activated protease, calpain, would cleave the cyclin-dependent kinase 5 (cdk5) activator p35 to a p25 fragment, which would lead to augmented cdk5 activity, and cdk5-mediated tau hyperphosphorylation. To test this hypothesis, we induced calpain-mediated p35 cleavage in rat hippocampal neuronal cultures and studied the relationship between p25 production, cdk5 activity, and tau phosphorylation. In glutamate-treated cells p35 was cleaved to p25 and this was associated with elevated cdk5 activity. However, tau phosphorylation was concomitantly decreased at multiple sites. The calpain inhibitor MDL28170 prevented the cleavage of p35 but had no effect on tau phosphorylation, suggesting that calpain-mediated processes, i.e., the cleavage of p35 to p25 and cdk5 activation, do not contribute to tau phosphorylation in these conditions. Treatment of the neuronal cultures with N-methyl-D-aspartic acid or with calcium ionophores resulted in an outcome highly similar to that of glutamate. We conclude that, in neuronal cells, the cleavage of p35 to p25 is associated with increased activity of cdk5 but not with tau hyperphosphorylation. (C) 2002 Elsevier Science (USA). All rights reserved.
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收藏
页码:693 / 698
页数:6
相关论文
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