Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.
Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.
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尿毒症血清中积累的 3-DG 在透析相关淀粉样变性中观察到晚期糖基化终产物对 β2m 的修饰。
作者：
T. Niwa;T. Katsuzaki;T. Momoi;T. Miyazaki;H. Ogawa;A. Saito;S. Miyazaki;K. Maeda;N. Tatemichi;Y. Takei
从透析相关性淀粉样变性（AAP）患者的淀粉样沉积物中分离的β 2微球蛋白（β 2 m）已被证明被晚期糖基化终产物（AGEs）修饰。我们用单克隆抗AGE抗体通过免疫组化证实AGE定位于淀粉样沉积物。为了阐明β 2 m-淀粉样蛋白的AGE修饰机制，我们研究了3-脱氧葡萄糖酮（3-DG），一种有效的蛋白交联的中间体的美拉德反应，对β 2 m的AGE修饰的影响，并定量血液透析（HD）和持续非卧床腹膜透析（CAPD）患者和未透析患者的血清3-DG水平。尿毒症患者透析前后血清3-DG水平均明显升高。血透后血清3-DG水平虽有下降，平均下降率为67%，但仍明显高于正常血清水平。β 2 m与3-DG在37 ℃下孵育，发出AGE特有的荧光，并引起AGE修饰和β 2 m的二聚体形成，如使用用于免疫组织化学显示膀胱中AGE的相同单克隆抗AGE抗体的Western印迹所示。AGE修饰的β 2 m二聚体可以从患有糖尿病的患者的淀粉样组织中提取。与葡萄糖相比，3-DG与β 2 m形成AGE和二聚体的反应性更强、更快，氨基胍抑制3-DG与β 2 m形成AGE和二聚体。因此，尿毒症血清中3-DG的积累可能参与了β 2 m-淀粉样蛋白的AGE修饰。
beta 2microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGEs). We demonstrated that AGE was localized to amyloid deposits in patients with DRA by immunohistochemistry using a monoclonal anti-AGE antibody. To clarify the mechanism of AGE modification of beta 2m-amyloid, we studied the effects of 3-deoxyglucosone (3-DG), a potent protein crosslinking the intermediate of the Maillard reaction, on the AGE modification of beta 2m, and quantified the serum levels of 3-DG in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and undialyzed patients. The serum levels of 3-DG were markedly increased in the dialyzed and undialyzed uremic patients. Although the serum level of 3-DG decreased after HD with a mean reduction rate of 67%, it was still significantly higher than in normal serum. Incubation of beta 2m with 3-DG at 37 degrees C emitted fluorescence characteristic for AGE, and caused AGE modification and dimer formation of beta 2m as demonstrated by Western blotting using the same monoclonal anti-AGE antibody used for immunohistochemical demonstration of AGE in DRA. The AGE-modified dimer of beta 2m could be extracted from the amyloid tissue of a patient with DRA. 3-DG showed more intense and faster reactivity with beta 2m to form AGE and dimer as compared with glucose, and aminoguanidine suppressed the AGE and dimer formation of beta 2m by 3-DG. In conclusion, 3-DG accumulating in uremic serum may be involved in the AGE modification of beta 2m-amyloid.
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DOI：
10.1073/pnas.81.2.583
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MONNIER, VM;KOHN, RR;CERAMI, A
通讯作者：
CERAMI, A
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：
--
发表时间：
1989-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Sell;V. Monnier
通讯作者：
D. Sell;V. Monnier
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
胰岛素受体的配体依赖性内化和再循环。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Knutson,VP
通讯作者：
Knutson,VP