Taming apoptosis in peritoneal dialysis.
Excessive, insufficient, or untimely apoptosis may result in disorders of cell numbers. Peritoneal demesothelization is an example of disease by decreased cell number; untimely leukocyte apoptosis impairs peritoneal defense. Conventional peritoneal dialysis solutions accelerate neutrophil apoptosis. Glucose degradation products such as 3,4-dideoxyglucosone-3-ene (3,4-DGE) decisively contribute to apoptosis induced by these solutions, in both leukocytes and mesothelial cells and in both culture and peritoneal dialysis patients. Pan-caspase inhibition retards neutrophil apoptosis and improves peritoneal clearance of Staphylococcus aureus in animal models. However, regulation of apoptosis in mesothelial cells is more complex than in leukocytes, and caspase inhibitors may not be the optimal drugs to modulate apoptosis in these cells. In this regard, Bax antagonistic peptides protect mesothelial cells from 3,4-DGE. In addition, novel molecular targets have been identified. Short-term modulation of apoptosis may be useful to accelerate recovery and to prevent irreversible peritoneal injury following peritonitis.
Santamaria
Beatriz
B
Dialysis Unit, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Instituto Reina Sofía de Investigación Nefrológica, Universidad Autónoma de Madrid, Madrid, Spain.
Ucero
Alvaro Conrado
AC
Benito-Martin
Alberto
A
Selgas
Rafael
R
Ruiz-Ortega
Marta
M
Sanz
Ana B
AB
Egido
Jesús
J
Ortiz
Alberto
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015314:Dialysis Solutions / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000628:therapy; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D010538:Peritonitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011753:Pyrones / Q000009:adverse effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C504711:3,4-dideoxyglucosone-3-ene; D015314:Dialysis Solutions; D011753:Pyrones; D051028:bcl-2-Associated X Protein; D024981:Glycogen Phosphorylase