Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins.
Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins.
复制标题
磷酸化 p38MAPK 特异性抗体与肌氨酰不溶性过度磷酸化 tau 蛋白发生交叉反应。
DOI：
10.1111/j.1471-4159.2004.02558.x
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发表时间：
2004
影响因子：
4.7
通讯作者：
Yen,Shu-Hui
中科院分区：
文献类型：
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作者：
Sahara,Naruhiko;Vega,IrvingE;Ishizawa,Takashi;Lewis,Jada;McGowan,Eileen;Hutton,Michael;Dickson,Dennis;Yen,Shu-Hui
阿尔茨海默病和相关疾病中积累的神经元缠结（NFT）含有过度磷酸化的tau，并显示对各种激酶的活性形式的免疫反应性。为了了解p38 MAPK（丝裂原活化蛋白激酶）在NFT形成中的作用，我们研究了表达P301 L突变tau的tau蛋白病转基因（Tg）小鼠模型JNPL 3，以及通过JNPL 3与Tg 2576小鼠杂交产生的双基因小鼠TAPP。年龄匹配的非Tg小鼠（NTg）、野生型人tau Tg小鼠（JN 25）和Tg 2576小鼠用作对照。磷酸化p38 MAPK（活性形式）免疫反应性始终位于NFT和颗粒泡变性的JNPL 3和TAPP小鼠年龄大于5个月。 在2 - 11月龄小鼠的脊髓和脑切片中未检测到未磷酸化/总p38 MAPK，即使JNPL 3小鼠，而不是对照组，通过蛋白质印迹法检测到总p38 MAPK的年龄依赖性增加。来自患有tau蛋白病的小鼠和人类的脊髓/脑提取物被证明具有不显著量的活性p38 MAPK。然而，它们含有不溶于sarkosyl的抗活性p38 MAPK交叉反应蛋白，其大小与磷酸化tau相似。因此，抗活性p38 MAPK免疫沉淀物显示tau免疫反应性，但不是总p38 MAPK，抗tau免疫沉淀物显示活性p38 MAPK免疫反应性。总之，结果表明抗活性p38 MAPK抗体与磷酸化tau的交叉反应性是tau阳性包涵体的免疫标记的原因。
Neurofibrillary tangles (NFT) accumulated in Alzheimer's diseases and related disorders contain hyperphosphorylated tau and display immunoreactivity for active forms of various kinases. To understand the role of p38MAPK (mitogen‐activated protein kinase) in NFT formation, we have studied a transgenic (Tg) mouse model of tauopathy, JNPL3, that expresses P301L mutant tau, and bigenic mice, TAPP, generated by cross‐breeding of JNPL3 with Tg2576 mice. Age‐matched non‐Tg mice (NTg), wild‐type human tau Tg mice (JN25), and Tg2576 mice were used as controls. Phosphorylated p38MAPK (active form) immunoreactivity was consistently located in NFT and granulovaculolar degeneration in JNPL3 and TAPP mice older than 5 months of age. Unphosphorylated/total‐p38MAPK was not detectable in spinal cord and brain sections from 2‐ to 11‐month‐old mice, even though JNPL3 mice, but not controls had an age‐dependent increase of total‐p38MAPK by western blotting. Spinal cord/brain extracts from mice and human with tauopathy were demonstrated to have insignificant amount of active‐p38MAPK. However, they contained antiactive‐p38MAPK cross‐reactive proteins insoluble in sarkosyl and similar to phosphorylated tau in size. Consistently, antiactive‐p38MAPK immunoprecipitates displayed tau immunoreactivity, but not total‐p38MAPK, and antitau immunoprecipitates displayed active‐p38MAPK immunoreactivity. Together, the results indicate that the cross‐reactivity of antiactive‐p38MAPK antibody with phosphorylated tau is responsible for the immunolabeling of tau‐positive inclusion.