国家自然科学基金资助项目(30170221,30430270).
This work was supported by a grant from The National Natural Sciences Foundation of China (30170221,30430270).
磷酸化 tau 是阿尔茨海默病 (Alzheimer's disease , AD) 的特征性病理改变———神经原纤维缠结 (neurofibrillary tangles , NFTs) 的主要组成部分 . 最近的研究显示: NFT 存在 Glu391 和 Asp421 位点被截断的 tau 片段,然而, tau 蛋白的磷酸化是否会影响 caspase-3 的切割作用尚不清楚 . 首先纯化重组 tau 蛋白,然后利用蛋白激酶 A (PKA) 、钙 / 钙调蛋白依赖性蛋白激酶Ⅱ (CaMK Ⅱ ) 和乳鼠海马组织抽提液对其磷酸化,并用 caspase-3 对不同磷酸化的 tau 蛋白进行切割,比较 caspase-3 对非磷酸化和不同蛋白激酶磷酸化的 tau 蛋白的切割特性 . 结果显示:除切割非磷酸化 tau 蛋白外, caspase-3 在体外可分别切割被 PKA 、 CaMK Ⅱ和乳鼠海马组织抽提液磷酸化的 tau 蛋白 . 这一结果提示:磷酸化修饰的 tau 蛋白仍然是 caspase-3 的底物 .
It is reported recently that truncated tau at Glu391 and Asp421 presents in the patients of Alzheimer's disease (AD) brain, and caspase-3 is involved in tau truncation at Asp421. In vitro studies show that caspase-3 can cleaved tau only at Asp421 and the proteolytic cleavage of tau at Asp421 by caspase-3 generates a truncated tau fragment namely tau1-421, which enhances filament assembly in vitro. Expression of tau1-421 in neurons promotes apoptosis. It is not known that if phosphorylated tau is also a substrate of caspase-3. To understand the question, recombinant human tau protein was purified and phosphorylated with protein kinase A (PKA), calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ ) or kinases from newborn rat hippocampi extract, and then these different tau species were cleaven by caspase-3. It was demonstrated that tau phosphorylated by PKA, CaMK Ⅱ and newborn hippocampi extract is also cleaven by caspase-3. As the phosphorylated tau also can be cleaven by caspase-3, it was speculated that phosphorylation tau is still the substrate of caspase-3.
段 萍,李夏春,邓艳秋,张 蕲,王建枝. Caspase-3 对磷酸化 tau 蛋白截断作用的研究[J].生物化学与生物物理进展,2005,32(1):81-85
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