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...
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MDPI AG
2018-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/19/2/352 |
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| author | Seung Pil Yun Yeo Min Yoon Jun Hee Lee Minjee Kook Yong-Seok Han Seo Kyung Jung Sang Hun Lee |
| author_facet | Seung Pil Yun Yeo Min Yoon Jun Hee Lee Minjee Kook Yong-Seok Han Seo Kyung Jung Sang Hun Lee |
| author_sort | Seung Pil Yun |
| collection | DOAJ |
| 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 (PrPC) activation was assessed. We confirmed that PrPC 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 PrPC expression. Our study demonstrates that TUDCA protects MSCs against inflammation and apoptosis in ER stress by PrPC expression in response to P-cresol exposure. |
| first_indexed | 2024-04-13T05:10:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T05:10:17Z |
| publishDate | 2018-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8b6a6054c1a04ca094530396188dccf92022-12-22T03:01:03ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-01-0119235210.3390/ijms19020352ijms19020352Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion ProteinSeung Pil Yun0Yeo Min Yoon1Jun Hee Lee2Minjee Kook3Yong-Seok Han4Seo Kyung Jung5Sang Hun Lee6Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAInstitute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, KoreaDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USADepartment of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAInstitute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, KoreaInstitute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, KoreaInstitute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, KoreaMesenchymal 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 (PrPC) activation was assessed. We confirmed that PrPC 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 PrPC expression. Our study demonstrates that TUDCA protects MSCs against inflammation and apoptosis in ER stress by PrPC expression in response to P-cresol exposure.http://www.mdpi.com/1422-0067/19/2/352mesenchymal stem cellsP-cresoltauroursodeoxycholic acidcellular prion proteinreactive oxygen species |
| spellingShingle | Seung Pil Yun Yeo Min Yoon Jun Hee Lee Minjee Kook Yong-Seok Han Seo Kyung Jung Sang Hun Lee Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein International Journal of Molecular Sciences mesenchymal stem cells P-cresol tauroursodeoxycholic acid cellular prion protein reactive oxygen species |
| 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 | mesenchymal stem cells P-cresol tauroursodeoxycholic acid cellular prion protein reactive oxygen species |
| url | http://www.mdpi.com/1422-0067/19/2/352 |
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