title: Bcl-xL prevents peritoneal dialysis solution-induced leukocyte apoptosis.
abstract: Conventional glucose-containing peritoneal dialysis solutions (PDS) with a high glucose degradation product content accelerate leukocyte apoptosis and impair peritoneal defense. Mononuclear cells are less sensitive than neutrophils to PDS-induced apoptosis, suggesting that they may express antiapoptotic molecules. Since apoptosis induced by PDS requires Bax, we explored the role of an antiapoptotic protein of the same family, Bcl-xL, in PDS-induced apoptosis in cultured peripheral blood mononuclear cells and monocytic THP-1 cells. In these cells, conventional PDS decreased the expression of Bcl-xL protein with a temporal pattern compatible with their lethal effect. Inhibition of Bcl-xL also induced mononuclear cell apoptosis. A cell-permeable TAT-BH4 peptide that contains the BH4 domain of Bcl-xL prevented mononuclear cell apoptosis induced by PDS. These data suggest that Bcl-xL protects mononuclear cells from apoptosis induced by bioincompatible PDS and that Bcl-xL-like molecules should be explored to prolong leukocyte survival and potentiate peritoneal defense during peritonitis.
authors.affiliation: Dialysis Unit, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Instituto Reina Sofía de Investigación Nefrológica.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Santamaría
authors.forename: Alberto
authors.initials: A
authors.lastname: Benito-Martin
authors.forename: Alvaro Conrado
authors.initials: AC
authors.lastname: Ucero
authors.forename: Ana
authors.initials: A
authors.lastname: Reyero
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D015314:Dialysis Solutions / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010530:Peritoneal Dialysis; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D015314:Dialysis Solutions; D010455:Peptides; C540574:TAT-BH4 peptide; D051020:bcl-X Protein; D005947:Glucose