ADVANCED GLYCOSYLATION ENDPRODUCTS BLOCK THE ANTIPROLIFERATIVE EFFECT OF NITRIC-OXIDE - ROLE IN THE VASCULAR AND RENAL COMPLICATIONS OF DIABETES-MELLITUS
ADVANCED GLYCOSYLATION ENDPRODUCTS BLOCK THE ANTIPROLIFERATIVE EFFECT OF NITRIC-OXIDE - ROLE IN THE VASCULAR AND RENAL COMPLICATIONS OF DIABETES-MELLITUS
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DOI：
10.1172/jci115928
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发表时间：
1992-09-01
影响因子：
15.9
通讯作者：
BUCALA, R
中科院分区：
文献类型：
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作者：
HOGAN, M;CERAMI, A;BUCALA, R
晚期糖基化终产物（AGEs）在长寿命组织蛋白（如基底膜胶原蛋白）上积累，并与糖尿病的许多长期并发症有关。这些产物来源于葡萄糖衍生的席夫碱和Amadori产物，但经过一系列复杂的重排反应，最终形成蛋白质结合的荧光杂环。AGEs可以与一氧化氮（NO）反应并化学还原，一氧化氮是一种有效的内皮细胞衍生的血管扩张剂和抗增殖因子。由于间充质细胞增殖是糖尿病血管病和肾小球病的早期和特征性病变，我们研究了胶原结合的AGEs功能性灭活NO抗增殖作用的可能性。在模型细胞培养系统中，发现AGEs可以阻断NO的细胞抑制作用对主动脉平滑肌和肾系膜细胞的抑制作用。基底膜AGEs对内皮细胞源性NO的失活可能是伴随长期糖尿病的血管和肾脏疾病加速发展的共同途径。
Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen-bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long-term diabetes mellitus.