RT Journal Article
T1 3,4-Dideoxyglucosone-3-ene as a mediator of peritoneal demesothelization
A1 Santamaría, Beatriz
A1 Ucero Herrería, Álvaro Conrado
A1 Reyero, Ana
A1 Selgas, Rafael
A1 Ruíz Ortega, Marta
A1 Catalan, Marina
A1 Egido, Jesús
A1 Ortiz, Alberto
AB Background: The mesothelium contributes significantly to the functional, structural and homeostatic properties of the peritoneum. Bioincompatible peritoneal dialysis solutions contribute to mesothelial cell loss during chronic peritoneal dialysis. Cell death has been implicated in mesothelial cell loss, but the molecular mechanisms have not been adequately characterized. We now report the modulation of mesothelial cell death by the glucose degradation product 3,4-dideoxyglucosone-3-ene (3,4-DGE).Methods: Human mesothelial cells were cultured from the effluents of stable dialysis patients. Apoptosis was quantified in cultured mesothelial cells and in peritoneal effluents. Confocal microscopy and inhibitors were used to assess molecular mechanisms.Results: Peritoneal dialysis solutions with a high content of both glucose and glucose degradation products, but not those with low glucose degradation product content, induced mesothelial cell apoptosis and loss of cell viability in culture and in vivo. 3,4-DGE also induced mesothelial cell apoptosis. Apoptosis induced by peritoneal dialysis solutions and 3,4-DGE was associated with oligomerization of Bax at mitochondria and caspase activation. Bax antagonism prevented caspase activation, apoptosis and cell death. The pancaspase inhibitor zVAD was also protective.Conclusion: 3,4-DGE and peritoneal dialysis solutions with a high content in glucose degradation products induce mesothelial cell apoptosis by a Bax-dependent mechanism. This could contribute to chronic demesothelization in peritoneal dialysis.
PB Oxford University
SN 0931-0509
YR 2008
FD 2008-06-03
LK https://hdl.handle.net/20.500.14352/116745
UL https://hdl.handle.net/20.500.14352/116745
LA eng
NO Santamaría B, Ucero AC, Reyero A, Selgas R, Ruiz-Ortega M, Catalán M, Egido J, Ortiz A. 3,4-Dideoxyglucosone-3-ene as a mediator of peritoneal demesothelization. Nephrol Dial Transplant. 2008 Oct;23(10):3307-15
NO Ministerio de Ciencia y Tecnología (España)
NO Instituto de Salud Carlos III (España)
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 5 abr 2025