In:
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, SAGE Publications, Vol. 29, No. 1 ( 2009-01), p. 44-51
Abstract:
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/L 3,4-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 and p 〈 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). Conclusions 3,4-DGE promotes apoptosis in HPMCs by a caspase-related mechanism.
Type of Medium:
Online Resource
ISSN:
0896-8608
,
1718-4304
DOI:
10.1177/089686080902900107
Language:
English
Publisher:
SAGE Publications
Publication Date:
2009
detail.hit.zdb_id:
2075957-5
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