Yamagishi Sho-ichi, Amano Shinjiro, Inagaki Yosuke, Okamoto Tamami, Koga Kohachiro, Sasaki Nobuyuki, Yamamoto Hiroshi, Takeuchi Masayoshi, Makita Zenji
Division of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, 830-0011, Japan.
Biochem Biophys Res Commun. 2002 Jan 25;290(3):973-8. doi: 10.1006/bbrc.2001.6312.
The influence of advanced glycation end products (AGEs) on apoptotic cell death and vascular endothelial growth factor (VEGF) gene expression in cultured bovine retinal pericytes was investigated. When pericytes were incubated with three immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde, or glycolaldehyde, apoptotic cell death and DNA ladder formation were significantly induced. The cytopathic effects of glyceraldehyde- or glycolaldehyde-derived AGEs were significantly enhanced in AGE receptor-transfected pericytes. Furthermore, all of these AGEs were found to upregulate the secretory forms of VEGF mRNA levels in retinal pericytes. These results suggest that AGEs disturbed retinal microvascular homeostasis by inducing pericyte apoptosis and VEGF overproduction and thus were involved in the pathogenesis of early phase diabetic retinopathy.
研究了晚期糖基化终产物（AGEs）对培养的牛视网膜周细胞凋亡性细胞死亡和血管内皮生长因子（VEGF）基因表达的影响。当周细胞与三种免疫化学性质不同的AGEs一起孵育时，这些AGEs是通过将牛血清白蛋白与葡萄糖、甘油醛或乙醇醛在体外孵育制备的，可显著诱导凋亡性细胞死亡和DNA梯带形成。在转染了AGE受体的周细胞中，甘油醛或乙醇醛衍生的AGEs的细胞病变效应显著增强。此外，所有这些AGEs均被发现可上调视网膜周细胞中VEGF mRNA水平的分泌形式。这些结果表明，AGEs通过诱导周细胞凋亡和VEGF过度产生而扰乱视网膜微血管稳态，因此参与了早期糖尿病视网膜病变的发病机制。
