Hydroxyl radical mediates N-epsilon-(carboxymethyl)lysine formation from Amadori product

Hydroxyl radical mediates N-epsilon-(carboxymethyl)lysine formation from Amadori product
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DOI:
10.1006/bbrc.1997.6608
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发表时间:
1997-05-08
影响因子:
3.1
通讯作者:
Horiuchi, S
Horiuchi, S
中科院分区:
生物学4区
文献类型:
--
作者:
Nagai, R;Ikeda, K;Horiuchi, S

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最近的研究表明,N-羧甲基赖氨酸(CML)存在于几种组织蛋白中,蛋白质与葡萄糖孵育通过Schiff碱产生Amadori产物。Amadori产物的氧化裂解被认为是体内CML形成的主要途径,然而尚不清楚涉及哪种活性氧(ROS)。本研究是为了确定这样的ROS。我们制备了高度糖化的人血清白蛋白(HSA),其中含有高水平的Amadori产物,但检测不到CML水平。H_2O_2对糖基化HSA的CML形成有促进作用,而过氧化氢酶和甘露醇对CML的形成无抑制作用,而超氧化物歧化酶对CML的形成无影响。用Boc-果糖-赖氨酸作为Amadori模型化合物的实验也得到了类似的结果。这些数据表明,Fe ~(2+)与H_2O_2反应产生的羟基自由基介导Amadori化合物的CML形成。(C)北京:科学出版社.
Recent studies demonstrated N-epsilon-(carboxymethyl) lysine (CML) in several tissue proteins, Incubation of proteins with glucose leads through a Schiff base to Amadori products. Oxidative cleavage of Amadori products is considered as a major route to CML formation in vivo, whereas it is not known which reactive oxygen species (ROS) is involved. The present study is undertaken to identify such a ROS. We prepared heavily glycated human serum albumin (HSA) which contained a high level of Amadori products, but an undetectable level of CML. Incubation of glycated HSA with FeCl2, but not with H2O2, led to CML formation which was enhanced by H2O2, but inhibited by catalase or mannitol, whereas superoxide dismutase had no effect, Similar data were obtained by experiments using Boc-fructose-lysine as a model Amadori compound, These data indicate that hydroxyl radical generated by the reaction of Fe2+ with H2O2 mediates CML formation from Amadori compounds. (C) 1997 Academic Press.