Human peritoneal mesothelial cell death induced by high-glucose hypertonic solution involves Ca2+ and Na+ ions and oxidative stress with the participation of PKC/NOX2 and PI3K/Akt pathways

Felipe Simon, Pablo Tapia, Ricardo Armisen, Cesar Echeverria, Sebastian Gatica, Alejandro Vallejos, Alejandro Pacheco, Maria E. Sanhueza, Miriam Alvo, Erico Segovia, Rubén Torres

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

Original languageEnglish
Article number379
JournalFrontiers in Physiology
Volume8
Issue numberJUN
DOIs
Publication statusPublished - 13 Jun 2017

Keywords

  • Cell death
  • Dialysis
  • Hypertonicity
  • Mesothelial cell
  • Peritoneal tissue

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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