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https://hdl.handle.net/20.500.14094/90007941
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2024-04-25
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90007941 (fulltext)
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90007941
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open access
出版タイプ
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タイトル
Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study
著者
Matsuo, Kazuya ; Hosoda, Kohkichi ; Tanaka, Jun ; Yamamoto, Yusuke ; Imahori, Taichiro ; Nakai, Tomoaki ; Irino, Yasuhiro ; Shinohara, Masakazu ; Sasayama, Takashi ; Kohmura, Eiji
著者名
Matsuo, Kazuya
著者ID
A0793
研究者ID
1000090403261
著者名
Hosoda, Kohkichi
細田, 弘吉
ホソダ, コウキチ
所属機関名
大学院医学研究科 医科学専攻
著者名
Tanaka, Jun
著者名
Yamamoto, Yusuke
著者ID
A2355
研究者ID
1000030604277
著者名
Imahori, Taichiro
今堀, 太一郎
イマホリ, タイチロウ
所属機関名
医学部附属病院 脳神経外科
著者ID
A1534
研究者ID
1000060596089
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=c0c1e75c520f6e63520e17560c007669
著者名
Nakai, Tomoaki
中井, 友昭
ナカイ, トモアキ
所属機関名
医学研究科
著者ID
A1400
研究者ID
1000010415565
著者名
Irino, Yasuhiro
入野, 康宏
イリノ, ヤスヒロ
所属機関名
大学院医学研究科 医科学専攻
著者ID
A0846
研究者ID
1000080437483
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=7e44708e08ede856520e17560c007669
著者名
Shinohara, Masakazu
篠原, 正和
シノハラ, マサカズ
所属機関名
医学研究科
著者ID
A1382
研究者ID
1000010379399
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=b8758a4d12d875ed520e17560c007669
著者名
Sasayama, Takashi
篠山, 隆司
ササヤマ, タカシ
所属機関名
医学研究科
著者ID
A0460
研究者ID
1000030225388
著者名
Kohmura, Eiji
甲村, 英二
コウムラ, エイジ
所属機関名
大学院医学研究科 医科学専攻
収録物名
BMC Neuroscience
巻(号)
22(1)
ページ
9-9
出版者
BMC
刊行日
2021-02-08
公開日
2021-03-11
抄録
Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.
キーワード
Glucose-6-phosphate dehydrogenase
Heat shock protein
Metabolomics
Oxidative stress
Reperfusion injury
Stroke
カテゴリ
医学研究科
医学部附属病院
学術雑誌論文
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© The Author(s) 2021.
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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journal article
言語
English (英語)
eISSN
1471-2202
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NCID
AA12035336
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DOI
https://doi.org/10.1186/s12868-021-00614-7
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