Item type |
文献 / Documents(1) |
公開日 |
2024-10-07 |
アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
item_1722929371688 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0080843 |
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言語 |
ja |
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関連名称 |
10.1371/journal.pone.0080843 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
タイトル |
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タイトル |
Mitochondrial Dysfunction Leads to Deconjugation of Quercetin Glucuronides in Inflammatory Macrophages |
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言語 |
en |
タイトル別表記 |
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その他のタイトル |
Mechanism for Macrophage-Mediated Deconjugation |
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言語 |
en |
著者 |
Ishisaka, Akari
Kawabata, Kyuichi
Miki, Satomi
Shiba, Yuko
Minekawa, Shoko
Nishikawa, Tomomi
向井, 理恵
寺尾, 純二
Kawai, Yoshichika
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Dietary flavonoids, such as quercetin, have long been recognized to protect blood vessels from atherogenic inflammation by yet unknown mechanisms. We have previously discovered the specific localization of quercetin-3-O-glucuronide (Q3GA), a phase II metabolite of quercetin, in macrophage cells in the human atherosclerotic lesions, but the biological significance is poorly understood. We have now demonstrated the molecular basis of the interaction between quercetin glucuronides and macrophages, leading to deconjugation of the glucuronides into the active aglycone. In vitro experiments showed that Q3GA was bound to the cell surface proteins of macrophages through anion binding and was readily deconjugated into the aglycone. It is of interest that the macrophage-mediated deconjugation of Q3GA was significantly enhanced upon inflammatory activation by lipopolysaccharide (LPS). Zymography and immunoblotting analysis revealed that β-glucuronidase is the major enzyme responsible for the deglucuronidation, whereas the secretion rate was not affected after LPS treatment. We found that extracellular acidification, which is required for the activity of β-glucuronidase, was significantly induced upon LPS treatment and was due to the increased lactate secretion associated with mitochondrial dysfunction. In addition, the β-glucuronidase secretion, which is triggered by intracellular calcium ions, was also induced by mitochondria dysfunction characterized using antimycin-A (a mitochondrial inhibitor) and siRNA-knockdown of Atg7 (an essential gene for autophagy). The deconjugated aglycone, quercetin, acts as an anti-inflammatory agent in the stimulated macrophages by inhibiting the c-Jun N-terminal kinase activation, whereas Q3GA acts only in the presence of extracellular β-glucuronidase activity. Finally, we demonstrated the deconjugation of quercetin glucuronides including the sulfoglucuronides in vivo in the spleen of mice challenged with LPS. These results showed that mitochondrial dysfunction plays a crucial role in the deconjugation of quercetin glucuronides in macrophages. Collectively, this study contributes to clarifying the mechanism responsible for the anti-inflammatory activity of dietary flavonoids within the inflammation sites. |
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言語 |
en |
bibliographic_information |
en : PLOS ONE
巻 8,
号 11,
p. e80843,
発行日 2013-11-19
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収録物ID |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
19326203 |
出版者 |
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出版者 |
PLOS |
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言語 |
en |
item_10001_rights_15 |
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言語 |
en |
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権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
item_1723180141928 |
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識別子 |
279478 |
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識別子タイプ |
URI |
言語 |
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言語 |
eng |