title: High-dialysate-glucose-induced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells.
abstract: Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM, and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Hung
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 106, Taiwan ; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Shin-Yun
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kuan-Tien General Hospital, Taichung 433, Taiwan.
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Yang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan ; Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Tien-Ling
authors.initials: TL
authors.lastname: Liao
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Kao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D015314:Dialysis Solutions / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010537:Peritoneum / Q000166:cytology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015314:Dialysis Solutions; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D005947:Glucose; D000111:Acetylcysteine