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KMID : 0354720070310020105
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Journal of Korean Diabetes Association
2007 Volume.31 No. 2 p.105 ~ p.112
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Mechanism of 2-Deoxy-D-ribose-induced Damage in Pancreatic β-cells
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Koh Gwan-Pyo
Woo Jeong-Taek
Lee Dae-Ho
Oh Seung-Joon
Kim Sung-Woon
Kim Jin-Woo
Kim Young-Seol
Park Deok-Bae
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Abstract
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Background: Mechanism for glucose toxicity is known to be an increased oxidative stress produced by multiple pathways. In our previous report, 2-deoxy-d-ribose (dRib) promoted apoptosis by increasing oxidative stress in a pancreatic β-cell line. We performed this study to investigate the mechanism of dRib-induced damage of β-cells.
Methods: HIT-T15 cells were cultured in RPMI-1640 medium with 40 mM dRib for 24 hours after pretreatment with various concentrations of a metal chelator (DTPA) and inhibitors of protein glycation (aminoguanidine and pyridoxamine). Cell viability was determined by MTT assay. Apoptosis was analyzed by flow cytometry with annexin V/PI double staining.
Results: DTPA, which inhibits the monosaccharide autoxidation, partially reversed dRib-induced cytotoxicity
in a dose-dependent manner (P < 0.01). The cytotoxicity was also suppressed dose-dependently by aminoguanidine (AG) and pyridoxamine (PM) (P < 0.05 and P < 0.01, repectively). Flow cytometric analysis showed that pretreatment of DTPA and AG also reversed the dRib-triggered apoptosis in a dose-dependent manner. We assessed the additional protective effects of inhibitors of protein glycation from dRib-induced cytotoxiciy in the presence of a metal chelator. The additions of AG (P < 0.05) and PM (P < 0.01) significantly reduced the cytotoxicity compared with DTPA alone group.
Conclusion: This results suggest that dRib produce cytotoxicity and apoptosis through the mechanisms of
advanced glycation endproducts (AGEs) formation including the monsaccharide autoxidation and protein glycation in pancreatic β-cell. Thus, dRib could be a surrogate for glucose in the study of glucose toxicity and chronic diabetic complications.
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KEYWORD
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Autoxidation, Glucose toxicity, Oxidative stress, Protein glycation, β-cell apoptosis, 2-deoxy-D-ribose
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