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小鼠脑单体乙酰胆碱酯酶的发育调控

Developmental regulation of mouse brain monomeric acetylcholinesterase.

作者信息

Moreno R D, Campos F O, Dajas F, Inestrosa N C

机构信息

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

Int J Dev Neurosci. 1998 Apr;16(2):123-34. doi: 10.1016/s0736-5748(98)00008-2.

Abstract

Acetylcholinesterase (AChE) molecular forms were studied during mouse brain development. Mouse embryos expressed a monomeric (G1) and a tetrameric (G4) AChE form. Our results indicate that G4 AChE expressed at embryonic day (ED) 9 and ED15 could be purified by acridinium-Sepharose chromatography and shared similar biochemical and kinetic properties with the adult form. However, the G1 form expressed at either embryonic stage did not bind to acridinium, was not inhibited by excess substrate, and possessed higher K(m) and lower Vmax values than the adult G1 form. Two peripheral anionic binding site inhibitors, fasciculin and propidium, had a significantly lower affinity for the monomeric form at ED9. Results are discussed in terms of the biological significance of the embryonic G1 form, and its resemblance to the AChE activity found, associated with the senile plaques present in the brains of Alzheimer's patients.

摘要

在小鼠大脑发育过程中对乙酰胆碱酯酶(AChE)的分子形式进行了研究。小鼠胚胎表达一种单体形式(G1)和一种四聚体形式(G4)的AChE。我们的结果表明,在胚胎第9天(ED9)和第15天(ED15)表达的G4 AChE可通过吖啶鎓 - 琼脂糖层析法纯化,并且与成年形式具有相似的生化和动力学特性。然而,在任一胚胎阶段表达的G1形式不与吖啶鎓结合,不受过量底物抑制,并且与成年G1形式相比具有更高的K(m)值和更低的Vmax值。两种外周阴离子结合位点抑制剂,束丝菌素和碘化丙啶,对ED9时的单体形式具有显著更低的亲和力。根据胚胎G1形式的生物学意义及其与在阿尔茨海默病患者大脑中存在的老年斑相关的AChE活性的相似性对结果进行了讨论。

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