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阿尔茨海默β/A4淀粉样前体蛋白的加工：受调节蛋白磷酸化的试剂调控

Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation.

作者信息

Buxbaum J D, Gandy S E, Cicchetti P, Ehrlich M E, Czernik A J, Fracasso R P, Ramabhadran T V, Unterbeck A J, Greengard P

机构信息

Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.

出版信息

Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003-6. doi: 10.1073/pnas.87.15.6003.

DOI:10.1073/pnas.87.15.6003
PMID:2116015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC54458/
Abstract

The turnover and processing of the Alzheimer beta/A4 amyloid precursor protein (beta APP) has been studied in PC12 cells after treatment with agents that regulate protein phosphorylation. Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the levels of 15- and 19-kDa peptides. These peptides appeared to be COOH-terminal fragments of beta APP, which arose when phorbol 12,13-dibutyrate increased the rate of proteolytic processing of mature forms of beta APP. Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, also led to decreased levels of mature beta APP and increased levels of the 15- and 19-kDa peptides. H-7, an inhibitor of protein kinase C and of several other protein kinases, apparently decreased the rate of proteolytic processing of mature beta APP. The sizes of the putative COOH-terminal fragments observed after treatment with either phorbol 12,13-dibutyrate or okadaic acid suggest that one or both may contain the entire beta/A4 region of beta APP and thus be amyloidogenic. Our results support the hypothesis that abnormal protein phosphorylation may play a role in the development of the cerebral amyloidosis that accompanies Alzheimer disease.

摘要

在用调节蛋白磷酸化的试剂处理PC12细胞后，对阿尔茨海默β/A4淀粉样前体蛋白（β-淀粉样前体蛋白）的周转和加工进行了研究。佛波醇12,13 - 二丁酸酯是一种刺激蛋白激酶C的试剂，它降低了成熟β-淀粉样前体蛋白的水平，并增加了15 kDa和19 kDa肽段的水平。这些肽段似乎是β-淀粉样前体蛋白的COOH末端片段，当佛波醇12,13 - 二丁酸酯提高成熟形式的β-淀粉样前体蛋白的蛋白水解加工速率时产生。冈田酸是蛋白磷酸酶1和2A的抑制剂，它也导致成熟β-淀粉样前体蛋白水平降低以及15 kDa和19 kDa肽段水平增加。H - 7是蛋白激酶C和其他几种蛋白激酶的抑制剂，它明显降低了成熟β-淀粉样前体蛋白的蛋白水解加工速率。用佛波醇12,13 - 二丁酸酯或冈田酸处理后观察到的假定COOH末端片段的大小表明，其中一个或两个片段可能包含β-淀粉样前体蛋白的整个β/A4区域，因此具有淀粉样变性。我们的结果支持这样一种假说，即异常的蛋白磷酸化可能在伴随阿尔茨海默病的脑淀粉样变性的发展中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/6dc884da788c/pnas01040-0426-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/7740c62e1174/pnas01040-0425-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/7a9914688513/pnas01040-0425-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/5dc9f1db908e/pnas01040-0426-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/6dc884da788c/pnas01040-0426-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/7740c62e1174/pnas01040-0425-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/7a9914688513/pnas01040-0425-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/5dc9f1db908e/pnas01040-0426-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fd/54458/6dc884da788c/pnas01040-0426-b.jpg

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本文引用的文献

1
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Nature. 1984;308(5961):693-8. doi: 10.1038/308693a0.
2
Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.一种编码阿尔茨海默病脑淀粉样蛋白的cDNA的特性及染色体定位
Science. 1987 Feb 20;235(4791):877-80. doi: 10.1126/science.3810169.
3
Decreased levels of protein kinase C in Alzheimer brain.阿尔茨海默病患者大脑中蛋白激酶C水平降低。
阿尔茨海默病：β-淀粉样蛋白引发致病事件的分子视角
Biomedicines. 2021 Sep 1;9(9):1126. doi: 10.3390/biomedicines9091126.
4
Phosphorylation Signaling in APP Processing in Alzheimer's Disease.阿尔茨海默病中 APP 处理的磷酸化信号转导。
Int J Mol Sci. 2019 Dec 27;21(1):209. doi: 10.3390/ijms21010209.
5
Decrease in p3-Alcβ37 and p3-Alcβ40, products of Alcadein β generated by γ-secretase cleavages, in aged monkeys and patients with Alzheimer's disease.衰老猴子和阿尔茨海默病患者中，由γ-分泌酶切割产生的阿尔卡迪蛋白β产物p3-Alcβ37和p3-Alcβ40减少。
Alzheimers Dement (N Y). 2019 Nov 7;5:740-750. doi: 10.1016/j.trci.2019.09.015. eCollection 2019.
6
Cell Signaling with Extracellular Thioredoxin and Thioredoxin-Like Proteins: Insight into Their Mechanisms of Action.细胞外硫氧还蛋白和硫氧还蛋白样蛋白的信号转导：对其作用机制的深入了解。
Oxid Med Cell Longev. 2017;2017:8475125. doi: 10.1155/2017/8475125. Epub 2017 Sep 12.
7
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8
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9
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4
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5
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6
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8
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9
Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.编码脑血管和神经炎性斑块淀粉样肽的cDNA的分子克隆与特性分析。
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10
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