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Polyubiquitination Events Mediate Polymethylmethacrylate (PMMA) Particle Activation of NF-κB Pathway
https://asahikawa-med.repo.nii.ac.jp/records/4009
https://asahikawa-med.repo.nii.ac.jp/records/4009b07c14db-1393-4b99-b0d6-128b0d678f03
名前 / ファイル | ライセンス | アクション |
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4468.pdf (568.4 kB)
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Item type | 学術雑誌論文 / Journal Article_02(1) | |||||
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公開日 | 2012-05-17 | |||||
タイトル | ||||||
タイトル | Polyubiquitination Events Mediate Polymethylmethacrylate (PMMA) Particle Activation of NF-κB Pathway | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
山中, 康裕
× 山中, 康裕× Karuppaiah, Kannan× Abu-Ame, Yousef |
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書誌情報 |
Journal of Biological Chemistry 巻 286, 号 27, p. 23735-23741, 発行日 2011-07-01 |
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ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0021-9258 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1074/jbc.M111.223669 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The pathologic response to implant wear-debris constitutes a major component of inflammatory osteolysis and remains under intense investigation. Polymethylmethacrylate (PMMA) particles, which are released during implant wear and loosening, constitute a major culprit by virtue of inducing inflammatory and osteolytic responses by macrophages and osteoclasts, respectively. Recent work by several groups has identified important cellular entities and secreted factors that contribute to inflammatory osteolysis. In previous work, we have shown that PMMA particles contribute to inflammatory osteolysis through stimulation of major pathways in monocytes/macrophages, primarily NF-κB and MAP kinases. The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKKγ/NEMO. We have shown recently that interfering with the NF-κB and MAPK activation pathways, through introduction of inhibitors and decoy molecules, impedes PMMA-induced inflammation and osteolysis in mouse models of experimental calvarial osteolysis and inflammatory arthritis. In this study, we report that PMMA particles activate the upstream transforming growth factor β-activated kinase-1 (TAK1), which is a key regulator of signal transduction cascades leading to activation of NF-κB and AP-1 factors. More importantly, we found that PMMA particles induce TAK1 binding to NEMO and UBC13. In addition, we show that PMMA particles induce TRAF6 and UBC13 binding to NEMO and that lack of TRAF6 significantly attenuates NEMO ubiquitination. Altogether, these observations suggest that PMMA particles induce ubiquitination of NEMO, an event likely mediated by TRAF6, TAK1, and UBC13. Our findings provide important information for better understanding of the mechanisms underlying PMMA particle-induced inflammatory responses. | |||||
言語 | en | |||||
注記 | ||||||
内容記述タイプ | Other | |||||
内容記述 | © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. | |||||
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内容記述タイプ | Other | |||||
内容記述 | text | |||||
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出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
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内容記述タイプ | Other | |||||
内容記述 | application/pdf | |||||
ID(XooNIps) | ||||||
値 | 21566132 | |||||
閲覧数(XooNIps) | ||||||
値 | 1037 | |||||
ダウンロード数(XooNIps) | ||||||
値 | 547 |