2-Deoxy-D-ribose induces cellular damage by increasing oxidative stress and protein glycation in a pancreatic beta-cell line.
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.
Koh
Gwanpyo
G
Department of Internal Medicine, Jeju National University School of Medicine, Jeju 690-756, Republic of Korea. okdom@jejunu.ac.kr
Lee
Dae-Ho
DH
Woo
Jeong-Taek
JT
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003855:Deoxyribose / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D004369:Pentetic Acid / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D011733:Pyridoxamine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017304:Annexin A5; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D006146:Guanidines; D017382:Reactive Oxygen Species; D003855:Deoxyribose; D011733:Pyridoxamine; D004369:Pentetic Acid; C004479:pimagedine