title: Peritoneal dialysis fluid activates calcium signaling and apoptosis in mesothelial cells.
abstract: A larger diffusion of peritoneal dialysis (PD) is limited by the progressive deterioration of the dialysis membrane structure and function, characterized in vitro and in vivo by mesothelial cell loss and closely related to the use of bioincompatible dialysis solutions. The apoptosis rate of rat and human mesothelial cells incubated in commercial PD fluid (PDF, 4.25 g/dL dextrose) became significant as early as 1 h after PDF addition and reached a plateau at 4-5 h. This pattern was unchanged after exposure to 1.5 g/dL dextrose PDF or freshly prepared PDF, indicating that effects were independent on the dextrose strength and manufacturing procedures but strictly dependent on PDF composition. Molecular studies revealed that PDF exposure inactivated the physiological volume recovery from hypertonic shrinkage, accompanied by an abnormal Ca(2+) signaling: a progressive intracellular Ca(2+) ([Ca(2+)](i)) rise resulting from an increased Ca(2+) entry. PDF also affected cytoskeleton integrity: early dissolution of actin filaments occurred well before the appearance of typical apoptosis features. Lastly, the PDF dependent apoptosis was almost completely prevented by the contemporary Ca(2+) concentration decrease and K(+) addition. This study suggests that the PDF dependent apoptosis arises from the extreme volume perturbations in mesothelial cells, turned out unable to regulate their volume back once exposed to a hyperosmolal medium containing high Ca(2+) levels in the absence of K(+), such PDF.
authors.affiliation: Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Boccellino
authors.forename: Raffaele
authors.initials: R
authors.lastname: La Porta
authors.forename: Mario
authors.initials: M
authors.lastname: Coppola
authors.forename: Pasquale
authors.initials: P
authors.lastname: Petronella
authors.forename: Fulvio
authors.initials: F
authors.lastname: Freda
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderaro
authors.forename: Lucio
authors.initials: L
authors.lastname: Quagliuolo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D015314:Dialysis Solutions / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007583:Jejunum / Q000166:cytology; D009852:Omentum / Q000166:cytology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D051381:Rats
chemical_list: D015314:Dialysis Solutions; D002118:Calcium