Modification of beta 2-microglobulin with D-glucose or 3-deoxyglucosone inhibits A beta 2M amyloid fibril extension in vitro.
Modification of beta 2-microglobulin with D-glucose or 3-deoxyglucosone inhibits A beta 2M amyloid fibril extension in vitro.
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用 D-葡萄糖或 3-脱氧葡萄糖醛酮修饰 β2-微球蛋白可在体外抑制 Aβ2M 淀粉样原纤维延伸。
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
F. Gejyo
中科院分区：
文献类型：
--
作者：
N. Hashimoto;H. Naiki;F. Gejyo
β 2-微球蛋白（β 2 M）是沉积在A β 2 M淀粉样变性患者体内的淀粉样纤维（fA β 2 M）的主要成分。近年来，β 2 M和fA β 2 M的晚期糖基化终产物（AGE）在A β 2 M淀粉样变性的发病机制中起重要作用。我们首先表征了fA β 2 M的AGE修饰状态。用单克隆抗AGE抗体进行的Western印迹分析表明，纯化的fA β 2 M天然被AGE修饰。淀粉样沉积组织的免疫组化研究显示，淀粉样沉积物中AGE修饰区域呈斑片状分布。然后我们用D-葡萄糖或3-脱氧葡萄糖醛酮（3-DG）修饰β 2-m，并利用最近建立的fA β 2 M体外延伸的一级动力学模型研究这些修饰对fA β 2 M体外延伸的影响。Western印迹分析和酶联免疫吸附试验与单克隆抗AGE抗体表明，这些糖修饰的β 2 M含有AGE。在37 ° C下将fA β 2 M与天然β 2-m孵育期间，硫磺素T的荧光增加而没有滞后期并进行平衡。相反，在fA β 2 M与糖修饰的β 2 M孵育期间，仅观察到荧光略微增加。此外，糖修饰的β 2 M对fA β 2 M与天然β 2 M的延伸反应表现出剂量依赖性抑制作用。这些结果可能提示，在某些体内情况下，AGE对β 2-m的修饰可能对fA β 2 M的形成起抑制作用。
beta 2-microglobulin (beta 2M) is a major constituent of amyloid fibrils (fA beta 2M) deposited in patients with A beta 2M amyloidosis. Recently, advanced glycation end products (AGE) of beta 2M and fA beta 2M have been suggested to play an important role in the pathogenesis of A beta 2M amyloidosis. We first characterized the states of AGE modification of fA beta 2M. Western blot analysis with a monoclonal anti-AGE antibody showed that purified fA beta 2M was naturally modified with AGE. Immunohistochemical studies of amyloid-deposited tissue have revealed a patchy distribution of the AGE-modified area in the amyloid deposits. Then we modified beta 2-m either with D-glucose or with 3-deoxyglucosone (3-DG) and investigated the effect of these modification on fA beta 2M extension in vitro, using the recently established first-order kinetic model of fA beta 2M extension in vitro. Western blot analysis and enzyme linked immunosorbent assay with a monoclonal anti-AGE antibody showed that these sugar-modified beta 2M contained AGE. During the incubation of fA beta 2M with native beta 2-m at 37 degrees C, the fluorescence of thioflavin T increased without a lag phase and proceeded to equilibrium. On the contrary, only a slight increase in fluorescence was observed during the incubation of fA beta 2M with sugar-modified beta 2M. Moreover, sugar-modified beta 2M exhibited a dose-dependent inhibitory effect on the extension reaction of fA beta 2M with native beta 2M. These results may suggest that in some in vivo situations, the modification of beta 2-m with AGE could play an inhibitory role for the formation of fA beta 2M.
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从完整的β2-微球蛋白体外形成淀粉样原纤维。
DOI：
10.1016/0006-291x(85)90198-6
发表时间：
1985
影响因子：
3.1
作者：
Connors,LH;Shirahama,T;Skinner,M;Fenves,A;Cohen,AS
通讯作者：
Cohen,AS
DOI：
10.1073/pnas.93.6.2353
发表时间：
1996-03-19
影响因子：
11.1
作者：
Miyata, T;Taneda, S;Monnier, VM
通讯作者：
Monnier, VM
DOI：
10.1016/s0021-9258(17)36966-1
发表时间：
1994-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
通讯作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
DOI：
10.1016/s0021-9258(19)50004-7
发表时间：
1992-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
N. Araki;N. Ueno;B. Chakrabarti;Y. Morino;S. Horiuchi
通讯作者：
N. Araki;N. Ueno;B. Chakrabarti;Y. Morino;S. Horiuchi
DOI：
10.1016/0006-291x(85)91948-5
发表时间：
1985-01-01
影响因子：
3.1
作者：
GEJYO, F;YAMADA, T;SCHMID, K
通讯作者：
SCHMID, K