Okawa Yasuhiro, Ishiguro Koichi, Fujita Shinobu C
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
FEBS Lett. 2003 Jan 30;535(1-3):183-9. doi: 10.1016/s0014-5793(02)03883-8.
We previously showed that starvation causes reversible hyperphosphorylation of tau in the mouse brain. To explore possible involvement of stress in tau hyperphosphorylation quantitative analysis of phosphorylated tau in four brain regions of mice subjected to cold water stress (CWS) was made by immunoblot analyses using phosphorylation-dependent antibodies directed to eight sites on tau known to be hyperphosphorylated in the brain of Alzheimer's disease (AD) patients. Ser199, Ser202/Thr205, Thr231/Ser235 were hyperphosphorylated 20 and 40 min after CWS. The response was pronounced in the hippocampus and cerebral hemisphere, but weak in the cerebellum in parallel with the regional vulnerability in AD. Among the regulatory phosphorylation of protein kinases studied, a transient phosphorylation of tau protein kinase I/glycogen synthase kinase 3beta at Ser9 was most conspicuous.
我们之前表明饥饿会导致小鼠大脑中tau蛋白发生可逆性的过度磷酸化。为了探究应激可能参与tau蛋白过度磷酸化的情况，我们使用针对tau蛋白上已知在阿尔茨海默病（AD）患者大脑中发生过度磷酸化的八个位点的磷酸化依赖性抗体，通过免疫印迹分析对遭受冷水应激（CWS）的小鼠四个脑区中磷酸化tau蛋白进行了定量分析。在CWS后20分钟和40分钟，Ser199、Ser202/Thr205、Thr231/Ser235发生了过度磷酸化。这种反应在海马体和大脑半球中很明显，但在小脑里很微弱，这与AD中的区域易损性情况相似。在所研究的蛋白激酶的调节性磷酸化中，tau蛋白激酶I/糖原合酶激酶3β在Ser9处的瞬时磷酸化最为显著。
