3,4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis.
BACKGROUND
Heat-sterilized, single-chambered, glucose-containing peritoneal dialysis solutions promote neutrophil apoptosis and impair the peritoneal antibacterial response. It has been proposed that glucose degradation products may be responsible for this effect. However, the precise contribution of individual glucose degradation products had not been addressed.


METHODS
The effect of individual glucose degradation products on apoptosis in cultured human neutrophils and peripheral blood mononuclear cells was studied.


RESULTS
Peritoneal dialysis solutions with a high content of both glucose and glucose degradation products accelerated neutrophil and mononuclear cell apoptosis. Among the different glucose degradation products, 3,4-di-deoxyglucosone-3-ene (3,4-DGE) accelerated apoptosis in neutrophils and peripheral blood mononuclear cells at concentrations (25 micromol/L) in the range found in heat-sterilized, single-chambered, 4.25% glucose peritoneal dialysis fluids. Apoptosis induced by 3,4-DGE was caspase-dependent and could be prevented by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk). By contrast, no cytotoxicity was observed following the addition of methylglyoxal, acetaldehyde, formaldehyde, or 3-deoxyglucosone at concentrations found in peritoneal dialysis solutions.


CONCLUSIONS
3,4-DGE appears to be the main proapoptotic factor in high glucose peritoneal dialysis solutions. 3,4-DGE may impair peritoneal defenses by accelerating leukocyte apoptosis.
Catalan
Marina Penélope
MP
Unidad de Dialisis, Fundacion Jimenez Diaz, Universidad Autónoma de Madrid, Instituto Reina Sofia de Investigación Nefrológica, Madrid, Spain.
Santamaría
Beatriz
B
Reyero
Ana
A
Ortiz
Arturo
A
Egido
Jesús
J
Ortiz
Alberto
A
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D015314:Dialysis Solutions; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000628:therapy*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010530:Peritoneal Dialysis; D010538:Peritonitis / Q000276:immunology; D011753:Pyrones / Q000494:pharmacology*
C504711:3,4-dideoxyglucosone-3-ene; D015314:Dialysis Solutions; D011753:Pyrones; D020169:Caspases; D005947:Glucose