Glucose-induced changes in the phenotype of human peritoneal mesothelial cells: Effect of L-2-oxothiazolidine carboxylic acid

Andrzej Brẽborowicz, Maciej Brẽborowicz, Dimitrios G. Oreopoulos

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: During peritoneal dialysis, mesothelial cells are chronically exposed to high concentrations of glucose. Therefore, the cytotoxic effect of glucose may alter the function and reactivity of these cells. Methods: For 4 weeks, human peritoneal mesothelial cells were cultured in vitro in medium supplemented with 45 mM glucose or 45 mM mannitol or with 45 mM glucose and 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTZ), the latter being a precursor for glutathione synthesis. Peroxidation of the mesothelial cell lipids, synthetic activity and reaction of these cells to peritoneal dialysis fluids were studied. Results: In contrast to mannitol, glucose enhanced the peroxidation of the cellular lipids (+65%, p < 0.01) an effect that was prevented by OTZ. Synthesis of hyaluron-an and vascular endothelial growth factor was reduced in mesothelial cells treated with glucose by 36% (p < 0.01) and 44% (p < 0.05), respectively; both glucose effects were reversed when cells were incubated with glucose plus OTZ. Monocyte chemoattractant protein-1 synthesis by cells exposed to glucose was increased by 31% (p < 001), and again that effect was prevented by OTZ. Glucose and mannitol stimulated synthesis of fi-bronectin (+32%, p < 0.05). Mesothelial cells chronically exposed to glucose became activated after subsequent exposure to the dialysis fluid, as reflected by the increased release of interleukin (IL)-6, in contrast to control mesothelial cells, in which IL-6 synthesis was suppressed. Conclusions: Chronic exposure of mesothelial cells to glucose changes their synthetic activity and their reaction after exposure to dialysis fluids. Some of these effects are prevented by OTZ, which suggests that glucose-induced free radicals are responsible for a change in mesothelial cell phenotype under the conditions of peritoneal dialysis.

Original languageEnglish (US)
Pages (from-to)471-476
Number of pages6
JournalAmerican Journal of Nephrology
Volume23
Issue number6
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Carboxylic Acids
Phenotype
Glucose
Peritoneal Dialysis
Mannitol
Dialysis
Interleukin-6
Artificial Cells
Chemokine CCL2
Ascitic Fluid
Vascular Endothelial Growth Factor A
Lipid Peroxidation
Free Radicals
Glutathione
Cultured Cells

Keywords

  • Free radicals
  • Glucose, high concentrations
  • L-2-oxothiazolidine- 4-carboxylic acid
  • Mesothelium

ASJC Scopus subject areas

  • Nephrology

Cite this

Glucose-induced changes in the phenotype of human peritoneal mesothelial cells : Effect of L-2-oxothiazolidine carboxylic acid. / Brẽborowicz, Andrzej; Brẽborowicz, Maciej; Oreopoulos, Dimitrios G.

In: American Journal of Nephrology, Vol. 23, No. 6, 2003, p. 471-476.

Research output: Contribution to journalArticle

Brẽborowicz, Andrzej ; Brẽborowicz, Maciej ; Oreopoulos, Dimitrios G. / Glucose-induced changes in the phenotype of human peritoneal mesothelial cells : Effect of L-2-oxothiazolidine carboxylic acid. In: American Journal of Nephrology. 2003 ; Vol. 23, No. 6. pp. 471-476.
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AU - Brẽborowicz, Andrzej

AU - Brẽborowicz, Maciej

AU - Oreopoulos, Dimitrios G.

PY - 2003

Y1 - 2003

N2 - Background: During peritoneal dialysis, mesothelial cells are chronically exposed to high concentrations of glucose. Therefore, the cytotoxic effect of glucose may alter the function and reactivity of these cells. Methods: For 4 weeks, human peritoneal mesothelial cells were cultured in vitro in medium supplemented with 45 mM glucose or 45 mM mannitol or with 45 mM glucose and 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTZ), the latter being a precursor for glutathione synthesis. Peroxidation of the mesothelial cell lipids, synthetic activity and reaction of these cells to peritoneal dialysis fluids were studied. Results: In contrast to mannitol, glucose enhanced the peroxidation of the cellular lipids (+65%, p < 0.01) an effect that was prevented by OTZ. Synthesis of hyaluron-an and vascular endothelial growth factor was reduced in mesothelial cells treated with glucose by 36% (p < 0.01) and 44% (p < 0.05), respectively; both glucose effects were reversed when cells were incubated with glucose plus OTZ. Monocyte chemoattractant protein-1 synthesis by cells exposed to glucose was increased by 31% (p < 001), and again that effect was prevented by OTZ. Glucose and mannitol stimulated synthesis of fi-bronectin (+32%, p < 0.05). Mesothelial cells chronically exposed to glucose became activated after subsequent exposure to the dialysis fluid, as reflected by the increased release of interleukin (IL)-6, in contrast to control mesothelial cells, in which IL-6 synthesis was suppressed. Conclusions: Chronic exposure of mesothelial cells to glucose changes their synthetic activity and their reaction after exposure to dialysis fluids. Some of these effects are prevented by OTZ, which suggests that glucose-induced free radicals are responsible for a change in mesothelial cell phenotype under the conditions of peritoneal dialysis.

AB - Background: During peritoneal dialysis, mesothelial cells are chronically exposed to high concentrations of glucose. Therefore, the cytotoxic effect of glucose may alter the function and reactivity of these cells. Methods: For 4 weeks, human peritoneal mesothelial cells were cultured in vitro in medium supplemented with 45 mM glucose or 45 mM mannitol or with 45 mM glucose and 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTZ), the latter being a precursor for glutathione synthesis. Peroxidation of the mesothelial cell lipids, synthetic activity and reaction of these cells to peritoneal dialysis fluids were studied. Results: In contrast to mannitol, glucose enhanced the peroxidation of the cellular lipids (+65%, p < 0.01) an effect that was prevented by OTZ. Synthesis of hyaluron-an and vascular endothelial growth factor was reduced in mesothelial cells treated with glucose by 36% (p < 0.01) and 44% (p < 0.05), respectively; both glucose effects were reversed when cells were incubated with glucose plus OTZ. Monocyte chemoattractant protein-1 synthesis by cells exposed to glucose was increased by 31% (p < 001), and again that effect was prevented by OTZ. Glucose and mannitol stimulated synthesis of fi-bronectin (+32%, p < 0.05). Mesothelial cells chronically exposed to glucose became activated after subsequent exposure to the dialysis fluid, as reflected by the increased release of interleukin (IL)-6, in contrast to control mesothelial cells, in which IL-6 synthesis was suppressed. Conclusions: Chronic exposure of mesothelial cells to glucose changes their synthetic activity and their reaction after exposure to dialysis fluids. Some of these effects are prevented by OTZ, which suggests that glucose-induced free radicals are responsible for a change in mesothelial cell phenotype under the conditions of peritoneal dialysis.

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KW - Glucose, high concentrations

KW - L-2-oxothiazolidine- 4-carboxylic acid

KW - Mesothelium

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