Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal
Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal
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DOI：
10.1016/s0003-9861(02)00067-x
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发表时间：
2002-06-01
影响因子：
3.9
通讯作者：
Padayatti, PS
中科院分区：
文献类型：
--
作者：
Nagaraj, RH;Sarkar, P;Padayatti, PS
美拉德反应产生的晚期糖基化终末产物(AGEs)有助于蛋白质老化以及AGE和糖尿病相关并发症的发病机制。甲基乙二醛(MG)是糖基化终末产物合成的重要中间体，近年来的研究表明吡哆胺可抑制晚期糖基化产物和脂氧化产物的形成。我们想要确定吡哆胺是否可以抑制MG介导的美拉德反应，从而防止AGE的形成。当晶状体蛋白与MG在37℃、pH 7.4的条件下孵育时，我们发现吡哆胺对甲基乙醛衍生的AGEs的形成有抑制作用，且呈浓度依赖性。吡哆胺可降低红细胞和血浆中的MG水平，阻止糖尿病大鼠血浆蛋白中甲基乙醛赖氨酸二聚体的形成，并阻止戊糖苷(一种源于糖的AGE)在血浆蛋白中形成。吡哆胺还可减少糖尿病大鼠血浆蛋白中蛋白质羰基和硫代巴比妥酸反应物质的形成。吡哆胺治疗不能恢复糖尿病动物的红细胞谷胱甘肽(减少了近一半)，但它提高了红细胞乙二醛酶I的活性。我们分离了MG与吡哆胺反应的主要产物，并将其鉴定为甲基乙醛-吡哆胺二聚体。我们的研究表明，吡哆胺可以减少氧化应激和AGE的形成。我们怀疑吡哆胺与MG的直接相互作用是AGE抑制的部分原因。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
Advanced glycation end products (AGEs) from the Maillard reaction contribute to protein aging and the pathogenesis of age-and diabetes-associated complications. The alpha-dicarbonyl compound methylglyoxal (MG) is an important intermediate in AGE synthesis, Recent studies suggest that pyridoxamine inhibits formation of advanced glycation and lipoxidation products. We wanted to determine if pyridoxamine could inhibit MG-mediated Maillard reactions and thereby prevent AGE formation. When lens proteins were incubated with MG at 37degreesC, pH 7.4, we found that pyridoxamine inhibits formation of methylglyoxal-derived AGEs concentration dependently. Pyridoxamine reduces MG levels in red blood cells and plasma and blocks formation of methylglyoxallysine dimer in plasma proteins from diabetic rats and it prevents pentosidine (an AGE derived from sugars) from forming in plasma proteins. Pyridoxamine also decreases formation of protein carbonyls and thiobarbituric-acid-reactive substances in plasma proteins from diabetic rats. Pyridoxamine treatment did not restore erythrocyte glutathione (which was reduced by almost half) in diabetic animals, but it enhanced erythrocyte glyoxalase I activity. We isolated a major product of the reaction between MG and pyridoxamine and identified it as methylglyoxal-pyridoxamine dimer. Our studies show that pyridoxamine reduces oxidative stress and AGE formation. We suspect that a direct interaction of pyridoxamine with MG partly accounts for AGE inhibition. (C) 2002 Elsevier Science (USA). All rights reserved.