徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.疾患酵素学研究センター(2007年4月1日〜2016年3月31日/->組織[徳島大学.先端酵素学研究所.次世代酵素学研究領域])

1. (英) Kim Mi Sun / (日) 金 善美

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2. 坂井 隆志

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3. (英) Dang Van Huy / (日) ダン ヴァン フイ / (読) だん ゔぁん ふぃー

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4. チャン ホアンナム([徳島大学.高等教育研究センター.学修支援部門]/[徳島大学.国際センター])

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5. 小野 公嗣

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6. 石村 和敬

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7. 福井 清([徳島大学])

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(英) Nucling, a novel protein associated with NF-B, regulates endotoxin-induced apoptosis in vivo

(英) Nucling is a proapoptotic protein that regulates the apoptosome and nuclear factor-kappa B (NF-B) signalling pathways. Strong stimuli, such as Gram-negative bacterial lipopolysaccharide (LPS), induce the simultaneous secretion of cytokines following the activation of NF-B. Proinflammatory cytokines can induce liver damage through several mechanisms such as increases in oxidative stress and apoptotic reactions leading to tissue necrosis. Herein, we show that Nucling-knockout (KO) mice are resistant to LPS that consistently caused mortality in wild-type (WT) counterparts. Although serum levels of cytokines such as tumour necrosis factor (TNF)-, interleukin (IL)-1 and IL-6 did not differ significantly between WT and Nucling-KO mice after the LPS challenge, hepatocytes of Nucling-KO mice were refractory to LPS- or TNF--induced cell death. These results were consistent with the decreased expression of proapoptotic proteins including apoptosis-inducing factor and cleaved form of poly (ADP-ribose) polymerase and terminal deoxynucleotidyl transferase dUTP nick end-labelling positive cells in the liver of Nucling-KO mice after the administration of a lethal dose of LPS. Moreover, the upregulation of NF-B-regulated anti-apoptotic molecules including cellular inhibitor of apoptosis (cIAP) 1 and cIAP2 was observed in the liver of Nucling-KO mice after LPS treatment. These findings indicate that the Nucling deficiency leads to resistance to apoptosis in liver. We propose that Nucling is important for the induction of apoptosis in cells damaged by cytotoxic stressors through the NF-B signalling pathway.

1. (英) Animals
2. アポトーシス(apoptosis)
3. (英) Apoptosis Regulatory Proteins
4. (英) Cells, Cultured
5. 細胞質分裂(cytokinesis)
6. (英) Disease Resistance
7. (英) Down-Regulation
8. (英) Endotoxins
9. (英) Hepatocytes
10. (英) Kupffer Cells
11. (英) Male
12. (英) Membrane Proteins
13. (英) Mice
14. ノックアウトマウス(knockout mice)
15. (英) NF-kappa B
16. (英) Shock, Septic
17. シグナル伝達(signal transduction)
18. (英) Specific Pathogen-Free Organisms
19. (英) Survival Analysis
20. (英) Survival Rate
21. (英) Up-Regulation

1. (英) Article.PublicationTypeList.PublicationType: Journal Article

2. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't