Antibody binding to cell surface amyloid precursor protein induces neuronal injury by deregulating the phosphorylation of focal adhesion signaling related proteins
Antibody binding to cell surface amyloid precursor protein induces neuronal injury by deregulating the phosphorylation of focal adhesion signaling related proteins
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与细胞表面淀粉样前体蛋白结合的抗体通过解除粘着斑信号相关蛋白的磷酸化来诱导神经元损伤
DOI：
10.1016/j.neulet.2009.09.022
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发表时间：
2009-11
影响因子：
2.5
通讯作者：
Xu, Yu-Xia
中科院分区：
文献类型：
--
作者：
Guo, Jing-Chun;Yan, Jie;Zhu, Cui-Qing;Sun, Xiao-Bo;Wang, Hong-Quan;Xu, Yu-Xia
Aβ的前体--全长淀粉样β蛋白前体（APP）的生物学功能尚未完全了解。越来越多的研究报道抗体与细胞表面APP结合导致神经元损伤。然而，细胞表面APP介导神经元损伤的机制仍有待确定。APP与整合素在细胞表面的共定位使我们推测，粘着斑（FA）相关机制参与了表面APP介导的神经元损伤。本研究结果表明，原代培养的神经元经抗APP-N-末端抗体处理后，不仅引起神经元损伤和突起形态学异常改变，而且引起FA蛋白反应出现急性先增加后减少的模式。此外，Src蛋白激酶抑制剂4-氨基-5-氨基-1，3-二氢吡啶（4-amino-5-amino-1，3-dimethyl（4-氯苯基）-7（叔丁基）吡唑（3，4-D）丙酰胺（PP 2）和G蛋白抑制剂百日咳毒素（PTX），这表明Src家族激酶和G蛋白在APP诱导的FA信号中起作用。此外，PTX和PP 2预处理能够抑制APP-抗体诱导的神经元损伤。总之，这些结果表明APP通过去调节FA信号介导神经元损伤的新机制。
The biological function of full-length amyloid-β protein precursor (APP), the precursor of Aβ, is not fully understood. Mounting studies reported that antibody binding to cell surface APP causes neuronal injury. However, the mechanism of cell surface APP mediating neuronal injury remains to be determined. Colocalization of APP with integrin on cell surface leads us to suppose that focal adhesion (FA) related mechanism is involved in surface APP-mediated neuronal injury. In the present study, results demonstrated that primary cultured neurons treated with antibody against APP-N-terminal not only caused neuronal injury and aberrant morphologic changes of neurite, but also induced reaction of FA proteins appearing an acute increase then decrease pattern. Moreover, the elevation of tyrosine phosphorylation of FA proteins including paxillin and focal adhesion kinase (FAK), and down-regulated expression of protein tyrosine phosphatase (PTP1B) induced by APP antibody were prevented by inhibitor of Src protein kinases 4-amino-5-(4-chlorophenyl)-7(t-butyl) pyrazol (3,4-D) pyramide (PP2) and G protein inhibitor pertussis toxin (PTX), implying that Src family kinase and G protein play roles in APP-induced FA signals. In addition, pretreatment with PTX and PP2 was able to suppress APP-antibody induced neuronal injury. Taken together, the results suggest a novel mechanism for APP mediating neuronal injury through deregulating FA signals.
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影响因子：
3.5
作者：
H. Sudo;Hong Jiang;T. Yasukawa;Y. Hashimoto;T. Niikura;M. Kawasumi;Shuji Matsuda;Y. Takeuchi
通讯作者：
H. Sudo;Hong Jiang;T. Yasukawa;Y. Hashimoto;T. Niikura;M. Kawasumi;Shuji Matsuda;Y. Takeuchi
影响因子：
6.1
作者：
Seung-Yong Yoon;Jung-Eun Choi;JuHee Yoon;J. Huh;Dong Hou Kim
通讯作者：
Seung-Yong Yoon;Jung-Eun Choi;JuHee Yoon;J. Huh;Dong Hou Kim
DOI：
10.1124/jpet.103.051383
发表时间：
2003-09-01
影响因子：
3.5
作者：
Hashimoto, Y;Niikura, T;Nishimoto, I
通讯作者：
Nishimoto, I
影响因子：
5.3
作者：
Uetsuki, T;Takemoto, K;Yoshikawa, K
通讯作者：
Yoshikawa, K
影响因子：
64.8
作者：
I. Nishimoto;T. Okamoto;Y. Matsuura;Shuji Takahashi;Toshimi Okamoto;Y. Murayama;E. Ogata
通讯作者：
I. Nishimoto;T. Okamoto;Y. Matsuura;Shuji Takahashi;Toshimi Okamoto;Y. Murayama;E. Ogata