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具有一份、两份或三份淀粉样前体蛋白（APP）基因的个体的成纤维细胞中的淀粉样前体蛋白代谢。

Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene.

作者信息

Racchi M, Johnston J A, Flood F M, Cowburn R F, Govoni S

机构信息

IRCCS 'Centro San Giovanni di Dio - Fatebenefratelli', Via Pilastroni 4, 25123 Brescia, Italy.

出版信息

Biochem J. 1999 Mar 15;338 ( Pt 3)(Pt 3):777-82.

PMID:10051452
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1220116/
Abstract

Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein.

摘要

在由于淀粉样前体蛋白（APP）基因存在一个、两个或三个拷贝而导致APP表达改变的天然模型中，研究了蛋白激酶C（PKC）激活对APP代谢的调节作用。我们发现，人皮肤成纤维细胞中APP的水平强烈影响PKC激活对可溶性APP（sAPP）释放的作用。因此，与对照个体的成纤维细胞相比，来自一名21号染色体缺失（包括APP基因座，Delta21）患者的成纤维细胞中APP mRNA和细胞相关APP的水平均较低，并且显示出佛波酯诱导的sAPP释放过度。相反，来自21三体唐氏综合征患者的成纤维细胞对佛波酯处理未表现出浓度依赖性反应。这些结果表明，APP表达水平可影响对PKC介导的该蛋白代谢调节的反应程度。

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本文引用的文献

1
Bradykinin-induced amyloid precursor protein secretion: a protein kinase C-independent mechanism that is not altered in fibroblasts from patients with sporadic Alzheimer's disease.缓激肽诱导的淀粉样前体蛋白分泌：一种不依赖蛋白激酶C的机制，在散发性阿尔茨海默病患者的成纤维细胞中未发生改变。
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Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts.阿尔茨海默病成纤维细胞中佛波酯刺激的β-淀粉样前体蛋白分泌存在缺陷。
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Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.与阿尔茨海默病老年斑中相似的分泌型淀粉样β蛋白，在体内会因与家族性阿尔茨海默病相关的早老素1和2以及APP突变而增加。
Nat Med. 1996 Aug;2(8):864-70. doi: 10.1038/nm0896-864.
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Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase C alpha.
J Biol Chem. 1993 Oct 5;268(28):21097-101.
9
Down syndrome--a gene dosage disease caused by trisomy of genes within a small segment of the long arm of chromosome 21, exemplified by the study of effects from the superoxide-dismutase type 1 (SOD-1) gene.唐氏综合征——一种由21号染色体长臂一小段内基因三体性导致的基因剂量疾病，以对1型超氧化物歧化酶（SOD-1）基因效应的研究为例。
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Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients.
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