Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins.
Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins.
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DOI：
10.1016/s0021-9258(17)36966-1
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发表时间：
1994-04
期刊：
影响因子：
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通讯作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
中科院分区：
文献类型：
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作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
在多种细胞/组织损伤中常见的活性氧中间产物的攻击，已被认为与糖尿病和其他血管疾病的发生有关。这种氧自由基可以由晚期糖基化终产物(AGEs)产生，AGEs是非酶糖化和氧化的蛋白质。由于AGEs的细胞相互作用是由特定的细胞结合蛋白、AGE受体(RAGE)和乳铁蛋白样多肽(LF-L)介导的，因此我们验证了AGE配体与RAGE和LF-L的复合体可以诱导氧化应激的假说。从糖尿病血浆中分离的AGE白蛋白或AGEs免疫可诱导内皮细胞(EC)氧化应激，包括硫代巴比妥酸反应物质(TBARS)的产生，并导致核因子-kappaB的激活，每一种激活都被AGE受体多肽抗体和抗氧化剂阻断。正常动物注射AGE白蛋白后，血管壁上出现丙二醛决定子，组织中TbARS增加，核因子-kappaB活化，血红素加氧酶基因表达增加。AGE受体/结合蛋白抗体或抗氧化剂可抑制AGE诱导的氧化应激。这些数据表明，AGEs与细胞靶点(如内皮细胞)的相互作用会导致氧化应激，导致基因表达和其他细胞特性的变化，从而可能导致血管病变的发生。需要进一步的研究来剖析氧化应激是发生在细胞表面还是发生在细胞内的某个位置。
Attack by reactive oxygen intermediates, common to many kinds of cell/tissue injury, has been implicated in the development of diabetic and other vascular diseases. Such oxygen-free radicals can be generated by advanced glycation end products (AGEs), which are nonenzymatically glycated and oxidized proteins. Since cellular interactions of AGEs are mediated by specific cellular binding proteins, receptor for AGE (RAGE) and the lactoferrin-like polypeptide (LF-L), we tested the hypothesis that AGE ligands tethered to the complex of RAGE and LF-L could induce oxidant stress. AGE albumin or AGEs immunoisolated from diabetic plasma resulted in induction of endothelial cell (EC) oxidant stress, including the generation of thiobarbituric acid reactive substances (TBARS) and resulted in the activation of NF-kappa B, each of which was blocked by antibodies to AGE receptor polypeptides and by antioxidants. Infusion of AGE albumin into normal animals led to the appearance of malondialdehyde determinants in the vessel wall and increased TBARS in the tissues, activation of NF-kappa B, and induction of heme oxygenase mRNA. AGE-induced oxidant stress was inhibited by pretreatment of animals with either antibodies to the AGE receptor/binding proteins or antioxidants. These data indicate that interaction of AGEs with cellular targets, such as ECs, leads to oxidant stress resulting in changes in gene expression and other cellular properties, potentially contributing to the development of vascular lesions. Further studies will be required to dissect whether oxidant stress occurs on the cell surface or at an intracellular locus.