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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/4009
b07c14db-1393-4b99-b0d6-128b0d678f03
名前 / ファイル ライセンス アクション
4468.pdf 4468.pdf (568.4 kB)
Item type 学術雑誌論文 / Journal Article_02(1)
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 journal article
著者 山中, 康裕

× 山中, 康裕

ja 山中, 康裕

ja-Kana ヤマナカ, ヤスヒロ

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Karuppaiah, Kannan

× Karuppaiah, Kannan

en Karuppaiah, Kannan

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Abu-Ame, Yousef

× Abu-Ame, Yousef

en 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
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
注記 © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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内容記述タイプ Other
資源タイプ text
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出版タイプ AM
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内容記述 application/pdf
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