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Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase
We previously reported the importance of induced nuclear transglutaminase (TG) 2 activity, which results in hepatic cell death, in ethanol-induced liver injury. Here, we show that co-incubation of either human hepatic cells or mouse primary hepatocytes derived from wild-type but not TG2(−/−) mice wi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500562/ https://www.ncbi.nlm.nih.gov/pubmed/28684792 http://dx.doi.org/10.1038/s41598-017-04630-8 |
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author | Shrestha, Ronak Shrestha, Rajan Qin, Xian-Yang Kuo, Ting-Fang Oshima, Yugo Iwatani, Shun Teraoka, Ryutaro Fujii, Keisuke Hara, Mitsuko Li, Mengqian Takahashi-Nakaguchi, Azusa Chibana, Hiroji Lu, Jun Cai, Muyi Kajiwara, Susumu Kojima, Soichi |
author_facet | Shrestha, Ronak Shrestha, Rajan Qin, Xian-Yang Kuo, Ting-Fang Oshima, Yugo Iwatani, Shun Teraoka, Ryutaro Fujii, Keisuke Hara, Mitsuko Li, Mengqian Takahashi-Nakaguchi, Azusa Chibana, Hiroji Lu, Jun Cai, Muyi Kajiwara, Susumu Kojima, Soichi |
author_sort | Shrestha, Ronak |
collection | PubMed |
description | We previously reported the importance of induced nuclear transglutaminase (TG) 2 activity, which results in hepatic cell death, in ethanol-induced liver injury. Here, we show that co-incubation of either human hepatic cells or mouse primary hepatocytes derived from wild-type but not TG2(−/−) mice with pathogenic fungi Candida albicans and C. glabrata, but not baker’s yeast Saccharomyces cerevisiae, induced cell death in host cells by enhancing cellular, particularly nuclear, TG activity. Further pharmacological and genetic approaches demonstrated that this phenomenon was mediated partly by the production of reactive oxygen species (ROS) such as hydroxyl radicals, as detected by a fluorescent probe and electron spin resonance. A ROS scavenger, N-acetyl cysteine, blocked enhanced TG activity primarily in the nuclei and inhibited cell death. In contrast, deletion of C. glabrata nox-1, which encodes a ROS-generating enzyme, resulted in a strain that failed to induce the same phenomena. A similar induction of hepatic ROS and TG activities was observed in C. albicans-infected mice. An antioxidant corn peptide fraction inhibited these phenomena in hepatic cells. These results address the impact of ROS-generating pathogens in inducing nuclear TG2-related liver injuries, which provides novel therapeutic targets for preventing and curing alcoholic liver disease. |
format | Online Article Text |
id | pubmed-5500562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55005622017-07-10 Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase Shrestha, Ronak Shrestha, Rajan Qin, Xian-Yang Kuo, Ting-Fang Oshima, Yugo Iwatani, Shun Teraoka, Ryutaro Fujii, Keisuke Hara, Mitsuko Li, Mengqian Takahashi-Nakaguchi, Azusa Chibana, Hiroji Lu, Jun Cai, Muyi Kajiwara, Susumu Kojima, Soichi Sci Rep Article We previously reported the importance of induced nuclear transglutaminase (TG) 2 activity, which results in hepatic cell death, in ethanol-induced liver injury. Here, we show that co-incubation of either human hepatic cells or mouse primary hepatocytes derived from wild-type but not TG2(−/−) mice with pathogenic fungi Candida albicans and C. glabrata, but not baker’s yeast Saccharomyces cerevisiae, induced cell death in host cells by enhancing cellular, particularly nuclear, TG activity. Further pharmacological and genetic approaches demonstrated that this phenomenon was mediated partly by the production of reactive oxygen species (ROS) such as hydroxyl radicals, as detected by a fluorescent probe and electron spin resonance. A ROS scavenger, N-acetyl cysteine, blocked enhanced TG activity primarily in the nuclei and inhibited cell death. In contrast, deletion of C. glabrata nox-1, which encodes a ROS-generating enzyme, resulted in a strain that failed to induce the same phenomena. A similar induction of hepatic ROS and TG activities was observed in C. albicans-infected mice. An antioxidant corn peptide fraction inhibited these phenomena in hepatic cells. These results address the impact of ROS-generating pathogens in inducing nuclear TG2-related liver injuries, which provides novel therapeutic targets for preventing and curing alcoholic liver disease. Nature Publishing Group UK 2017-07-06 /pmc/articles/PMC5500562/ /pubmed/28684792 http://dx.doi.org/10.1038/s41598-017-04630-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shrestha, Ronak Shrestha, Rajan Qin, Xian-Yang Kuo, Ting-Fang Oshima, Yugo Iwatani, Shun Teraoka, Ryutaro Fujii, Keisuke Hara, Mitsuko Li, Mengqian Takahashi-Nakaguchi, Azusa Chibana, Hiroji Lu, Jun Cai, Muyi Kajiwara, Susumu Kojima, Soichi Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title | Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title_full | Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title_fullStr | Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title_full_unstemmed | Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title_short | Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
title_sort | fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500562/ https://www.ncbi.nlm.nih.gov/pubmed/28684792 http://dx.doi.org/10.1038/s41598-017-04630-8 |
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