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GRIM-19は結核菌のZn^<2+>メタロプロテアーゼの標的であり、NLRP3インフラマソームの活性化に必須である
http://hdl.handle.net/20.500.12000/0002018035
http://hdl.handle.net/20.500.12000/0002018035ae705a6f-395f-4de7-9259-a8da246d30b1
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iken541abstract.pdf (787 KB)
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iken541review.pdf (1023 KB)
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iken541text.pdf (10.6 MB)
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Item type | 琉球大学リポジトリ登録用アイテムタイプ(1) | |||||||||
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公開日 | 2022-06-10 | |||||||||
タイトル | ||||||||||
タイトル | GRIM-19 is a target of mycobacterial Zn^<2+> metalloprotease 1 and indispensable for NLRP3 inflammasome activation | |||||||||
言語 | en | |||||||||
タイトル | ||||||||||
タイトル | GRIM-19は結核菌のZn^<2+>メタロプロテアーゼの標的であり、NLRP3インフラマソームの活性化に必須である | |||||||||
言語 | ja | |||||||||
作成者 |
藏根, 友美
× 藏根, 友美
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アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
権利情報 | ||||||||||
言語 | en | |||||||||
権利情報 | © 2021 Federation of American Societies for Experimental Biology | |||||||||
権利情報 | ||||||||||
言語 | en | |||||||||
権利情報Resource | https://creativecommons.org/licenses/by-nc/4.0/ | |||||||||
権利情報 | Creative Commons Attribution-NonCommercial 4.0 International | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | inflammasome | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | interleukin-1β | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | macrophages | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | mitochondria | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Mycobacterium tuberculosis | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn^<2+> metalloprotease 1 (Zmp1) is known to suppress interleukin (IL)-1β production by inhibiting caspase-1 resulting in phagosome maturation arrest. However, the molecular mechanism of caspase-1 inhibition by Zmp1 is still elusive. Here, we identified GRIM-19 (also known as NDUFA13), an essential subunit of mitochondrial respiratory chain complex I, as a novel Zmp1-binding protein. Using the CRISPR/Cas9 system, we generated GRIM-19 knockout murine macrophage cell line J774.1 and found that GRIM-19 is essential for IL-1β production during mycobacterial infection as well as in response to NLRP3 inflammasome-activating stimuli such as extracellular ATP or nigericin. We also found that GRIM-19 is required for the generation of mitochondrial reactive oxygen species and NLRP3-dependent activation of caspase-1. Loss of GRIM-19 or forced expression of Zmp1 resulted in a decrease in mitochondrial membrane potential. Our study revealed a previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1β production during mycobacterial infection. | |||||||||
言語 | en | |||||||||
出版者 | ||||||||||
言語 | ja | |||||||||
出版者 | 琉球大学 | |||||||||
出版者 | ||||||||||
言語 | en | |||||||||
出版者 | University of the Ryukyus | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
資源タイプ | ||||||||||
資源タイプ | doctoral thesis | |||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
出版タイプ | ||||||||||
出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
関連情報 | ||||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1096/fj.202101074RR | |||||||||
収録物識別子 | ||||||||||
収録物識別子タイプ | PISSN | |||||||||
収録物識別子 | 0892-6638 | |||||||||
収録物識別子 | ||||||||||
収録物識別子タイプ | EISSN | |||||||||
収録物識別子 | 1530-6860 | |||||||||
収録物名 | ||||||||||
言語 | en | |||||||||
収録物名 | FASEB Journal | |||||||||
書誌情報 |
巻 36, 号 1 |
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学位授与番号 | ||||||||||
学位授与番号 | 甲第541号 | |||||||||
学位名 | ||||||||||
学位名 | 博士(医学) | |||||||||
言語 | ja | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2022-03-18 | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子 | 18001 | |||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関名 | 琉球大学 | |||||||||
言語 | ja |