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Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein
Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of various diseases including chronic kidney disease (CKD). However, endoplasmic reticulum (ER) stress induced by ischemia in the area of application limits the integration and survival of MSCs in patients. In our study, we...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855574/ https://www.ncbi.nlm.nih.gov/pubmed/29370069 http://dx.doi.org/10.3390/ijms19020352 |
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author | Yun, Seung Pil Yoon, Yeo Min Lee, Jun Hee Kook, Minjee Han, Yong-Seok Jung, Seo Kyung Lee, Sang Hun |
author_facet | Yun, Seung Pil Yoon, Yeo Min Lee, Jun Hee Kook, Minjee Han, Yong-Seok Jung, Seo Kyung Lee, Sang Hun |
author_sort | Yun, Seung Pil |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of various diseases including chronic kidney disease (CKD). However, endoplasmic reticulum (ER) stress induced by ischemia in the area of application limits the integration and survival of MSCs in patients. In our study, we generated ER stress-induced conditions in MSCs using P-cresol. As P-cresol is a toxic compound accumulated in the body of CKD patients and induces apoptosis and inflammation through reactive oxygen species (ROS), we observed ER stress-induced MSC apoptosis activated by oxidative stress, which in turn resulted from ROS generation. To overcome stress-induced apoptosis, we investigated the protective effects of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs. In ER stress, TUDCA treatment of MSCs reduced ER stress-associated protein activation, including GRP78, PERK, eIF2α, ATF4, IRE1α, and CHOP. Next, to explore the protective mechanism adopted by TUDCA, TUDCA-mediated cellular prion protein (PrP(C)) activation was assessed. We confirmed that PrP(C) expression significantly increased ROS, which was eliminated by superoxide dismutase and catalase in MSCs. These findings suggest that TUDCA protects from inflammation and apoptosis in ER stress via PrP(C) expression. Our study demonstrates that TUDCA protects MSCs against inflammation and apoptosis in ER stress by PrP(C) expression in response to P-cresol exposure. |
format | Online Article Text |
id | pubmed-5855574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58555742018-03-20 Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein Yun, Seung Pil Yoon, Yeo Min Lee, Jun Hee Kook, Minjee Han, Yong-Seok Jung, Seo Kyung Lee, Sang Hun Int J Mol Sci Article Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of various diseases including chronic kidney disease (CKD). However, endoplasmic reticulum (ER) stress induced by ischemia in the area of application limits the integration and survival of MSCs in patients. In our study, we generated ER stress-induced conditions in MSCs using P-cresol. As P-cresol is a toxic compound accumulated in the body of CKD patients and induces apoptosis and inflammation through reactive oxygen species (ROS), we observed ER stress-induced MSC apoptosis activated by oxidative stress, which in turn resulted from ROS generation. To overcome stress-induced apoptosis, we investigated the protective effects of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs. In ER stress, TUDCA treatment of MSCs reduced ER stress-associated protein activation, including GRP78, PERK, eIF2α, ATF4, IRE1α, and CHOP. Next, to explore the protective mechanism adopted by TUDCA, TUDCA-mediated cellular prion protein (PrP(C)) activation was assessed. We confirmed that PrP(C) expression significantly increased ROS, which was eliminated by superoxide dismutase and catalase in MSCs. These findings suggest that TUDCA protects from inflammation and apoptosis in ER stress via PrP(C) expression. Our study demonstrates that TUDCA protects MSCs against inflammation and apoptosis in ER stress by PrP(C) expression in response to P-cresol exposure. MDPI 2018-01-25 /pmc/articles/PMC5855574/ /pubmed/29370069 http://dx.doi.org/10.3390/ijms19020352 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yun, Seung Pil Yoon, Yeo Min Lee, Jun Hee Kook, Minjee Han, Yong-Seok Jung, Seo Kyung Lee, Sang Hun Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title | Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title_full | Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title_fullStr | Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title_full_unstemmed | Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title_short | Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein |
title_sort | tauroursodeoxycholic acid protects against the effects of p-cresol-induced reactive oxygen species via the expression of cellular prion protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855574/ https://www.ncbi.nlm.nih.gov/pubmed/29370069 http://dx.doi.org/10.3390/ijms19020352 |
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