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阿尔茨海默病成纤维细胞黏附性降低:淀粉样β蛋白前体是否参与其中?

Decreased adhesiveness of Alzheimer's disease fibroblasts: is amyloid beta-protein precursor involved?

作者信息

Uéda K, Cole G, Sundsmo M, Katzman R, Saitoh T

机构信息

Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093.

出版信息

Ann Neurol. 1989 Mar;25(3):246-51. doi: 10.1002/ana.410250307.

DOI:10.1002/ana.410250307
PMID:2729915
Abstract

The adhesiveness of fibroblasts derived from Alzheimer's disease (AD) patients to a plastic substratum was assessed as the proportion of cells attached to a plastic dish bottom after a 30-minute incubation in culture medium of cells dissociated in ethylenediaminetetraacetic acid and was compared with the adhesiveness of normal fibroblasts from non-AD controls. It was found that the normal fibroblasts adhered better to plastic than did AD cells. This reduced adhesiveness was observed in fibroblasts derived from both sporadic and familial AD patients. Because of the possible involvement of amyloid beta-protein precursor (ABPP) in the process of cellular adhesion, the amount of ABPP messenger RNA was measured in these fibroblasts and was found to be decreased in the familial AD fibroblasts, although not in cells from sporadic AD patients. Furthermore, there were fewer molecules detected by an anti-ABPP antibody in conditioned media from familial AD fibroblasts as compared with media from control fibroblasts. Therefore, although it is possible that the reduced adhesiveness of familial AD fibroblasts may result from genetic deficits in ABPP gene expression, the reduced adhesiveness of sporadic AD fibroblasts most likely results from certain deficits in molecules other than the ABPP.

摘要

将来自阿尔茨海默病(AD)患者的成纤维细胞与塑料基质的粘附性评估为在乙二胺四乙酸中解离的细胞在培养基中孵育30分钟后附着于塑料培养皿底部的细胞比例,并与来自非AD对照的正常成纤维细胞的粘附性进行比较。发现正常成纤维细胞比AD细胞更好地粘附于塑料。在散发性和家族性AD患者来源的成纤维细胞中均观察到这种粘附性降低。由于淀粉样β蛋白前体(ABPP)可能参与细胞粘附过程,因此在这些成纤维细胞中测量了ABPP信使RNA的量,发现家族性AD成纤维细胞中的ABPP信使RNA量减少,尽管散发性AD患者的细胞中没有减少。此外,与对照成纤维细胞的培养基相比,家族性AD成纤维细胞的条件培养基中用抗ABPP抗体检测到的分子更少。因此,虽然家族性AD成纤维细胞粘附性降低可能是由于ABPP基因表达的遗传缺陷所致,但散发性AD成纤维细胞粘附性降低最可能是由于ABPP以外的某些分子缺陷所致。

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引用本文的文献

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Ionic and signal transduction alterations in Alzheimer's disease: relevance of studies on peripheral cells.阿尔茨海默病中的离子与信号转导改变:外周细胞研究的相关性
Mol Neurobiol. 1999 Oct-Dec;20(2-3):93-109. doi: 10.1007/BF02742436.
2
Negative transactivation of cAMP response element by familial Alzheimer's mutants of APP.淀粉样前体蛋白家族性阿尔茨海默病突变体对环磷酸腺苷反应元件的负反式激活作用
EMBO J. 1996 May 15;15(10):2468-75.
3
Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype.V642 APP突变体的表达导致细胞凋亡,呈现出与阿尔茨海默病相关的表型特征。
EMBO J. 1996 Feb 1;15(3):498-509.
4
Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth.氨基酸序列RERMS代表促进成纤维细胞生长的β淀粉样蛋白/A4蛋白前体的活性结构域。
J Cell Biol. 1993 May;121(4):879-86. doi: 10.1083/jcb.121.4.879.
5
Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease.阿尔茨海默病患者成纤维细胞内的钙离子动员发生改变。
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):534-8. doi: 10.1073/pnas.91.2.534.
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Evidence for lysosomal processing of amyloid beta-protein precursor in cultured cells.培养细胞中淀粉样β蛋白前体溶酶体加工的证据。
Neurochem Res. 1989 Oct;14(10):933-9. doi: 10.1007/BF00965926.
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Mechanism of Alzheimer's disease: arguments for a neurotransmitter-aluminium complex implication.阿尔茨海默病的发病机制:关于神经递质 - 铝复合物关联的论据
Neurochem Res. 1990 Dec;15(12):1239-45. doi: 10.1007/BF01208586.
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Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.阿尔茨海默型痴呆患者血清中纤维蛋白溶解酶活性缺乏。
Experientia. 1992 Jul 15;48(7):656-9. doi: 10.1007/BF02118312.
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Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.神经元分化过程中β-淀粉样前体蛋白表达增加,但不伴有分泌性切割。
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A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion.阿尔茨海默病淀粉样前体蛋白的一个含109个氨基酸的C末端片段包含一段促进细胞黏附的序列-RHDS-。
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