3,4-dideoxyglucosone-3-ene induces apoptosis in human peritoneal mesothelial cells

◆ Objective: Glucose degradation products (GDPs) are formed during heat sterilization and storage of peritoneal dialysis (PD) fluids. 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP. 3,4-DGE induces apoptosis in leukocytes and renal tubular epithelial cells. Our aim was to evaluate the apoptotic effects of 3,4-DGE on human peritoneal mesothelial cells (HPMCs). ◆ Methods: Primary cultured HPMCs were treated with 25 or 50 μmol/L3,4-DGE. MTT assay was used to determine cell viability. Apoptosis was measured using TUNEL assay and flow cytometry. Expressions of procaspase-3, Bax, and Bcl-2 were estimated by Western blot. Activity of caspase-3 was measured and the effect of the caspase inhibitor zVAD-fmk (Z-Val-Ala-DL-Asp-fluoromethylketone) was evaluated by TUNEL assay. ◆ Results: 3,4-DGE treatment accelerated cell death in HPMCs in a dose- and time-dependent manner. Treatment with 3,4-DGE (25 and 50 μmol/L) significantly increased apoptosis compared to control (p < 0.05 andp <0.01 respectively) by TUNEL assay. Flow cytometry showed treatment with 50 μmol/L 3,4-DGE significantly increased apoptosis compared to control (p < 0.05). Decreased expression of procaspase-3 and increased activity of caspase-3 were observed in the presence of 50 μmol/L 3,4-DGE compared to control and 25 μmol/L 3,4-DGE (p <0.05). 3,4-DGE-induced HPMC apoptosis was decreased after pretreatment with the pan-caspase inhibitor zVAD-fmk in the 50 μmol/L 3,4-DGE-treated group (p < 0.001). The ratio of Bcl-2 to Bax expression was decreased in the 25 μmol/-L and the 50 μmol/L 3,4-DGE-treated groups compared to control (p < 0.05). ◆ Conclusion: 3,4-DGE-promotes apoptosis in HPMCs by a caspase-related mechanism.