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Perit Dial Int 28(Supplement_5): 48-52
2008
© 2008 International Society for Peritoneal Dialysis
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Articles

Bcl-xL PREVENTS PERITONEAL DIALYSIS SOLUTION-INDUCED LEUKOCYTE APOPTOSIS

Beatriz Santamaría1, Alberto Benito–Martin1, Alvaro Conrado Ucero1, Ana Reyero1, Rafael Selgas2, Marta Ruiz–Ortega3, Jesús Egido1 and Alberto Ortiz1,a

Dialysis Unit1 Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Instituto Reina Sofía de Investigación Nefrológica; Servicio de Nefrología2 Hospital Universitario La Paz; Laboratory of Cellular Biology in Renal Diseases3 Universidad Autónoma de Madrid, Madrid, Spain

Footnotes

a All authors (except JE) belong to REDinREN (Red de Investigación Renal Española del Instituto de Salud Carlos III, RETICS 06/0016).

Correspondence to: A. Ortiz, Unidad de Diálisis, Fundación Jiménez Díaz, Av Reyes Católicos 2, 28040 Madrid, Spain. aortiz{at}fjd.es

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.

KEY WORDS: Apoptosis; Bcl-xL; monocyte.




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B. Santamaria, A. C. Ucero, A. Benito-Martin, R. Selgas, M. Ruiz-Ortega, A. B. Sanz, J. Egido, and A. Ortiz
TAMING APOPTOSIS IN PERITONEAL DIALYSIS
Perit. Dial. Int., February 1, 2009; 29(Supplement_2): S45 - S48.
[Abstract] [Full Text] [PDF]


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