Abundant type 10 17β-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model
Abundant type 10 17β-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model
复制标题
DOI：
10.1016/s0169-328x(02)00102-x
复制
发表时间：
2002-02-28
期刊：
影响因子：
--
通讯作者：
Yang, SY
中科院分区：
文献类型：
--
作者：
He, XY;Wen, GY;Yang, SY
从小鼠脑组织中克隆了小鼠10型17β-羟基类固醇脱氢酶(17beta-HSD10)的全长cDNA1个核苷酸序列信息，为准确推断该野生型酶的氨基酸序列提供了可能。对这种酶的序列和三维模型的比较表明，以前其他小组报道的结构带有截短或突变的氨基末端序列。将野生型酶的前11个残基与绿色荧光蛋白融合后，报告蛋白直接进入线粒体。因此，N-末端被确定为线粒体靶向信号，解释了小鼠酶的细胞内定位。这种酶通常与线粒体有关。与内质网不同的是，内质网相关的淀粉样β结合蛋白(ERAB)这个微不足道的名字让人联想到它。用其C端区制备兔抗17betaHSD10抗体后，免疫金电子显微镜显示，该酶在转BetaAPP基因小鼠的海马区突触线粒体中大量表达，而在正常对照小鼠中未见表达。这种酶的高水平可能会破坏突触中类固醇激素的动态平衡，并导致小鼠阿尔茨海默病模型中海马区的突触丢失。(C)2002 Elsevier Science B.V.保留所有权利。
A full-length cDNA of mouse type 10 17 beta-hydroxy steroid dehydrogenase (17beta-HSD10) was cloned from brain, representing the accurate nucleotide sequence information that rendered possible an accurate deduction of the amino acid sequence of the wild-type enzyme. A comparison of sequences and three-dimensional models of this enzyme revealed that structures previously reported by other groups carry either a truncated or mutated amino-terminal sequence. Fusion of the first 11 residues of the wild-type enzyme to the green fluorescent protein directed the reporter protein into mitochondria. Thus, the N-terminus was identified as a mitochondrial targeting signal that accounts for the intracellular localization of the mouse enzyme. This enzyme is normally associated with mitochondria. not with the endoplasmic reticulum as suggested by its trivial name 'endoplasmic reticulum-associated amyloid-beta biding protein (ERAB)'. After its C-terminal region was used to raise rabbit anti-17betaHSD10 antibodies, immunogold electron microscopy showed that an abundance of this enzyme could be found in hippocampal synaptic mitochondria of betaAPP transgenic mice, but not in normal controls. High levels of this enzyme may disrupt steroid hormone homeostasis in synapses and contribute to synapse loss in the hippocampus of the mouse Alzheimer's disease model. (C) 2002 Elsevier Science B.V. All rights reserved.