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 |
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タイトル |
Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons |
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言語 |
en |
作成者 |
Ishida, Keishi
Kotake, Yaichiro
Sanoh, Seigo
Ohta, Shigeru
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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 |
権利情報 |
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権利情報 |
© 2017 The Pharmaceutical Society of Japan |
主題 |
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主題Scheme |
Other |
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主題 |
lead |
主題 |
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主題Scheme |
Other |
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主題 |
glutamate receptor 2 |
主題 |
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主題Scheme |
Other |
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主題 |
neurotoxicity |
主題 |
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主題Scheme |
Other |
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主題 |
mitogen-activated protein kinase (MAPK) |
主題 |
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主題Scheme |
NDC |
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主題 |
490 |
内容記述 |
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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. |
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言語 |
en |
内容記述 |
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内容記述タイプ |
Other |
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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 |
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出版者 |
The Pharmaceutical Society of Japan |
言語 |
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言語 |
eng |
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 |
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 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
10.1248/bpb.b16-00784 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1248/bpb.b16-00784 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0918-6158 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1347-5215 |
収録物識別子 |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA10885497 |
開始ページ |
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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
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旧ID |
47060 |