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Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons

https://hiroshima.repo.nii.ac.jp/records/2006478
https://hiroshima.repo.nii.ac.jp/records/2006478
d7ece2f4-8e44-4c17-8b34-74c7d525b3eb
名前 / ファイル ライセンス アクション
BiolPhamBull_40_303.pdf BiolPhamBull_40_303.pdf (8.4 MB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2023-03-18
タイトル
タイトル Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons
言語 en
作成者 Ishida, Keishi

× Ishida, Keishi

en Ishida, Keishi

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Kotake, Yaichiro

× Kotake, Yaichiro

en Kotake, Yaichiro

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Sanoh, Seigo

× Sanoh, Seigo

en Sanoh, Seigo

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Ohta, Shigeru

× Ohta, Shigeru

en Ohta, Shigeru

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利情報
権利情報 © 2017 The Pharmaceutical Society of Japan
主題
主題Scheme Other
主題 lead
主題
主題Scheme Other
主題 glutamate receptor 2
主題
主題Scheme Other
主題 neurotoxicity
主題
主題Scheme Other
主題 mitogen-activated protein kinase (MAPK)
主題
主題Scheme NDC
主題 490
内容記述
内容記述 Lead is a persistent environmental pollutant and exposure to high environmental levels causes various deleterious toxicities, especially to the central nervous system (CNS). The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor that is devoid of the glutamate receptor 2 (GluR2) subunit is Ca2+-permeable, which increases the neuronal vulnerability to excitotoxicity. We have previously reported that long-term exposure of rat cortical neurons to lead acetate induces decrease of GluR2 expression. However, it is not clarified whether lead-induced GluR2 decrease is involved in neurotoxicity. Therefore, we investigated the contribution of GluR2 non-containing AMPA receptor to lead-induced neurotoxic events. Although the expression of four AMPA receptor subunits (GluR1, GluR2, GluR3, and GluR4) was decreased by lead exposure, the decrease in GluR2 expression was remarkable among four subunits. Lead-induced neuronal cell death was rescued by three glutamate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, a non-selective AMPA receptor blocker), MK-801 (N-methyl-D-aspartate (NMDA) receptor blocker), and 1-naphthyl acetyl spermine (NAS, a specific Ca2+-permeable AMPA receptor blocker). Lead exposure activated extracellular signal-regulated protein kinase (ERK) 1/2, which was significantly ameliorated by CNQX. In addition, lead exposure activated p38 mitogen-activated protein kinase (MAPK p38), and protein kinase C (PKC), which was partially ameliorated by CNQX. Our findings indicate that Ca2+-permeable AMPA receptors resulting from GluR2 decrease may be involved in lead-induced neurotoxicity.
言語 en
内容記述
内容記述タイプ Other
内容記述 This study was supported by JSPS KAKENHI (B) Grant Numbers 23310047 (to Y.K.), 15H02826 (to Y.K.), and a Grant-in-Aid for JSPS Fellows Number 14J06534 (to K.I.).
出版者
出版者 The Pharmaceutical Society of Japan
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
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
関連情報
識別子タイプ DOI
関連識別子 10.1248/bpb.b16-00784
関連情報
識別子タイプ DOI
関連識別子 https://doi.org/10.1248/bpb.b16-00784
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 0918-6158
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 1347-5215
収録物識別子
収録物識別子タイプ NCID
収録物識別子 AA10885497
開始ページ
開始ページ 303
書誌情報 Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin

巻 40, 号 3, p. 303-309, 発行日 2017-03-01
旧ID 47060
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