Kim Jaetaek, Son Jang-Won, Lee Jeong-An, Oh Yeon-Sahng, Shinn Soon-Hyun
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
J Korean Med Sci. 2004 Feb;19(1):95-100. doi: 10.3346/jkms.2004.19.1.95.
One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive alpha-dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 microM) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kappaB are involved in the apoptotic process.
早期糖尿病视网膜病变的组织病理学特征之一是周细胞丢失。有证据表明，体内周细胞的丢失是由凋亡介导的。然而，周细胞凋亡的根本原因尚未完全明确。本研究调查了甲基乙二醛（MGO），一种葡萄糖代谢产生的活性α-二羰基化合物，对牛视网膜周细胞凋亡性细胞死亡的影响。通过ELISA分析核小体间DNA片段化显示，MGO（200至800微摩尔）以浓度依赖性方式诱导凋亡。细胞内活性氧更早产生，抗氧化剂N-乙酰半胱氨酸可抑制MGO诱导的凋亡。检测到NF-κB激活和caspase-3活性增加。caspase-3抑制剂Z-DEVD-fmk或NF-κB抑制剂吡咯烷二硫代氨基甲酸盐也可抑制凋亡。这些数据表明，糖尿病中观察到的MGO水平升高可能通过氧化应激机制导致牛视网膜周细胞凋亡，并提示NF-κB的核激活参与了凋亡过程。
