Department of Internal Medicine, Jeju National University School of Medicine, Jeju 690-756, Republic of Korea.
Metabolism. 2010 Mar;59(3):325-32. doi: 10.1016/j.metabol.2009.07.028. Epub 2009 Sep 29.
2-Deoxy-D-ribose (dRib) is a sugar with a high reducing capacity. We previously reported that dRib induced damage in pancreatic beta-cells. The aim of this study was to investigate the mechanism of dRib-induced beta-cell damage. 2-Deoxy-D-ribose provoked cytotoxicity and apoptosis within 24 hours in HIT-T15 cells. Three antiglycating agents-diethylenetriaminepentaacetic acid, aminoguanidine, and pyridoxamine-dose dependently inhibited dRib-triggered cytotoxicity and significantly suppressed apoptosis induced by dRib. 2-Deoxy-d-ribose increased intracellular reactive oxygen species and protein carbonyl levels in a dose-dependent manner. Diethylenetriaminepentaacetic acid and aminoguanidine significantly reduced dRib-induced rises in intracellular reactive oxygen species. All 3 inhibitors decreased the production of intracellular protein carbonyls by dRib. On incubation with albumin, dRib increased dicarbonyl and advanced glycation end product formation. Aminoguanidine and pyridoxamine significantly decreased the dicarbonyl and advanced glycation end product augmentations. These results suggest that both oxidative stress and protein glycation are important mechanisms of dRib-induced damage in a pancreatic beta-cell line.
2-脱氧-D-核糖(dRib)是一种还原能力很强的糖。我们之前的研究报告表明,dRib 会导致胰岛β细胞损伤。本研究旨在探讨 dRib 诱导的β细胞损伤的机制。2-脱氧-D-核糖在 24 小时内引发 HIT-T15 细胞的细胞毒性和凋亡。三种糖基化抑制剂——二乙三胺五乙酸、氨基胍和吡哆胺——呈剂量依赖性抑制 dRib 触发的细胞毒性,并显著抑制 dRib 诱导的细胞凋亡。2-脱氧-D-核糖以剂量依赖的方式增加细胞内活性氧和蛋白质羰基水平。二乙三胺五乙酸和氨基胍显著降低了 dRib 诱导的细胞内活性氧的增加。三种抑制剂均降低了 dRib 引起的细胞内蛋白质羰基的产生。与白蛋白孵育时,dRib 增加了二羰基和糖基化终产物的形成。氨基胍和吡哆胺显著降低了二羰基和糖基化终产物的增加。这些结果表明,氧化应激和蛋白质糖化都是 2-脱氧-D-核糖诱导胰岛β细胞损伤的重要机制。