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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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.
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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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