Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.
Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.
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发表时间：
1997-02
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通讯作者：
Alan W. Stitt;Y. M. Li;T. Gardiner;R. Bucala;D. Archer;H. Vlassara
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作者：
Alan W. Stitt;Y. M. Li;T. Gardiner;R. Bucala;D. Archer;H. Vlassara
晚期糖基化终产物（AGEs），由蛋白质和脂质与还原糖的非酶糖基化形成，与许多糖尿病并发症有关；然而，它们在糖尿病视网膜病变中的作用在很大程度上仍然未知。最近的研究表明，age的细胞作用可能是由age特异性受体（AGE-R）介导的。我们在stz诱导的糖尿病后2、4和8个月以及注射AGE牛血清白蛋白2周的非糖尿病大鼠的视网膜血管中检测了AGEs和AGE- r成分R1和R2的免疫定位。采用多克隆或单克隆抗age抗体和重组AGE-R1和AGE-R2多克隆抗体，胰蛋白酶消化分离后检测视网膜血管树的免疫反应性（IR）。糖尿病患者2、4、8个月后，基底膜AGE IR逐渐升高。8个月时，视网膜血管的周细胞、平滑肌细胞和内皮细胞显示密集的细胞内AGE IR。与糖尿病组相比，AGE表位在大鼠周细胞和平滑肌细胞中染色最强烈，而在基底膜中染色较少。正常或牛血清白蛋白输注大鼠的视网膜AGE IR大部分呈阴性。AGE-R1和-R2与正常、糖尿病和age -灌注大鼠视网膜血管内皮细胞、周细胞和平滑肌细胞的age共定位，且这种分布在不同情况下没有变化。这些数据表明，AGEs首先在基底膜内积累，然后在细胞内积累，并与细胞AGE-Rs共定位。长期糖尿病或急性AGE输注与周细胞损伤相关的条件后，周细胞内出现显著的AGE沉积。age和AGE-Rs在视网膜细胞中的共定位表明可能存在致病意义的相互作用。
Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance.