MAILLARD REACTION-MEDIATED MOLECULAR DAMAGE TO EXTRACELLULAR-MATRIX AND OTHER TISSUE PROTEINS IN DIABETES, AGING, AND UREMIA
MAILLARD REACTION-MEDIATED MOLECULAR DAMAGE TO EXTRACELLULAR-MATRIX AND OTHER TISSUE PROTEINS IN DIABETES, AGING, AND UREMIA
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DOI：
10.2337/diab.41.2.s36
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发表时间：
1992-10-01
期刊：
影响因子：
7.7
通讯作者：
IBRAHIM, SA
中科院分区：
文献类型：
--
作者：
MONNIER, VM;SELL, DR;IBRAHIM, SA
最近在对晚期美拉德反应产物的结构阐明方面的进展使得可以专门探讨该反应在年龄和糖尿病相关并发症的发病机制中的作用。吡咯啉是一种葡萄糖衍生的晚期糖基化终末产物，已有多克隆和单抗针对其进行了研究。免疫组织化学定位研究表明，吡咯啉主要存在于糖尿病患者和老年非糖尿病患者肾小球和小动脉肾组织硬化的细胞外基质中。戊二胺和羧甲基赖氨酸是从葡萄糖和抗坏血酸中衍生出来的美拉德最终产物。此外，戊糖苷可以在氧化条件下由其他几种糖形成，体外研究表明，一种涉及戊糖的常见中间体是必要的前体分子。这些先进的美拉德产品中含量最高的通常是细胞外基质，但这些产品也存在于晶状体蛋白和周转迅速的蛋白质中，如血浆蛋白质。糖尿病，尤其是尿毒症，极大地催化了戊二胺的形成。这两种情况的特点都是加速白内障形成、动脉粥样硬化和神经病变，这表明晚期美拉德反应产物造成的分子损伤可能是它们发生发展的共同机制。
Recent progress in structure elucidation of products of the advanced Maillard reaction now allows probing specifically for the role of this reaction in the pathogenesis of age- and diabetes-related complications. Pyrraline is a glucose-derived advanced glycation end product against which polyclonal and monoclonal antibodies have been raised. Immunohistochemical localization studies revealed that pyrraline is found predominantly in the sclerosed extracellular matrix of glomerular and arteriolar renal tissues from both diabetic and aged nondiabetic individuals. Pentosidine and carboxymethyllysine are Maillard end products derived from both glucose and ascorbate. In addition, pentosidine can be formed from several other sugars under oxidative conditions, and in vitro studies suggest that a common intermediate involving a pentose is a necessary precursor molecule. The highest levels of these advanced Maillard products are generally found in the extracellular matrix, but these products are also present in lens proteins and in proteins with a fast turnover such as plasma proteins. Diabetes, and especially uremia, greatly catalyzes pentosidine formation. Both conditions are characterized by accelerated cataractogenesis, atherosclerosis, and neuropathy, suggesting that molecular damage by advanced Maillard reaction products may be a common mechanism in their development.