Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase
Abstract 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−/−...
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2017
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oai:doaj.org-article:717d1979a5004405b36e03531f2846902021-12-02T15:05:40ZFungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase10.1038/s41598-017-04630-82045-2322https://doaj.org/article/717d1979a5004405b36e03531f2846902017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04630-8https://doaj.org/toc/2045-2322Abstract 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.Ronak ShresthaRajan ShresthaXian-Yang QinTing-Fang KuoYugo OshimaShun IwataniRyutaro TeraokaKeisuke FujiiMitsuko HaraMengqian LiAzusa Takahashi-NakaguchiHiroji ChibanaJun LuMuyi CaiSusumu KajiwaraSoichi KojimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Ronak Shrestha Rajan Shrestha Xian-Yang Qin Ting-Fang Kuo Yugo Oshima Shun Iwatani Ryutaro Teraoka Keisuke Fujii Mitsuko Hara Mengqian Li Azusa Takahashi-Nakaguchi Hiroji Chibana Jun Lu Muyi Cai Susumu Kajiwara Soichi Kojima Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
| description |
Abstract 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 |
article |
| author |
Ronak Shrestha Rajan Shrestha Xian-Yang Qin Ting-Fang Kuo Yugo Oshima Shun Iwatani Ryutaro Teraoka Keisuke Fujii Mitsuko Hara Mengqian Li Azusa Takahashi-Nakaguchi Hiroji Chibana Jun Lu Muyi Cai Susumu Kajiwara Soichi Kojima |
| author_facet |
Ronak Shrestha Rajan Shrestha Xian-Yang Qin Ting-Fang Kuo Yugo Oshima Shun Iwatani Ryutaro Teraoka Keisuke Fujii Mitsuko Hara Mengqian Li Azusa Takahashi-Nakaguchi Hiroji Chibana Jun Lu Muyi Cai Susumu Kajiwara Soichi Kojima |
| author_sort |
Ronak Shrestha |
| title |
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_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_sort |
fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/717d1979a5004405b36e03531f284690 |
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