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High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells

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 functio...

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Autores principales: Hung, Kuan-Yu, Liu, Shin-Yun, Yang, Te-Cheng, Liao, Tien-Ling, Kao, Shu-Huei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026970/
https://www.ncbi.nlm.nih.gov/pubmed/24891925
http://dx.doi.org/10.1155/2014/642793
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author Hung, Kuan-Yu
Liu, Shin-Yun
Yang, Te-Cheng
Liao, Tien-Ling
Kao, Shu-Huei
author_facet Hung, Kuan-Yu
Liu, Shin-Yun
Yang, Te-Cheng
Liao, Tien-Ling
Kao, Shu-Huei
author_sort Hung, Kuan-Yu
collection PubMed
description 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.
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spelling pubmed-40269702014-06-02 High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells Hung, Kuan-Yu Liu, Shin-Yun Yang, Te-Cheng Liao, Tien-Ling Kao, Shu-Huei Oxid Med Cell Longev Research Article 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. Hindawi Publishing Corporation 2014 2014-05-05 /pmc/articles/PMC4026970/ /pubmed/24891925 http://dx.doi.org/10.1155/2014/642793 Text en Copyright © 2014 Kuan-Yu Hung et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hung, Kuan-Yu
Liu, Shin-Yun
Yang, Te-Cheng
Liao, Tien-Ling
Kao, Shu-Huei
High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title_full High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title_fullStr High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title_full_unstemmed High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title_short High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells
title_sort high-dialysate-glucose-induced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026970/
https://www.ncbi.nlm.nih.gov/pubmed/24891925
http://dx.doi.org/10.1155/2014/642793
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