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

Duk Hyun Lee, Soon Youn Choi, Hye Myung Ryu, Chan Duck Kim, Sun Hee Park, Ho Young Chung, In San Kim, Yong Lim Kim

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

◆ 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.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalPeritoneal Dialysis International
Volume29
Issue number1
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • 3,4-DGE
  • Apoptosis
  • Caspase
  • Peritoneal mesothelial cells

ASJC Scopus subject areas

  • Nephrology

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