Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons
Biological and Pharmaceutical Bulletin 40 巻 3 号
303-309 頁
2017-03-01 発行
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| ファイル情報(添付) | |
| タイトル ( eng ) |
Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons
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| 作成者 |
Ishida Keishi
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| 収録物名 |
Biological and Pharmaceutical Bulletin
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| 巻 | 40 |
| 号 | 3 |
| 開始ページ | 303 |
| 終了ページ | 309 |
| 抄録 |
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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| 著者キーワード |
lead
glutamate receptor 2
neurotoxicity
mitogen-activated protein kinase (MAPK)
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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.).
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| NDC分類 |
医学 [ 490 ]
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| 言語 |
英語
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| 資源タイプ | 学術雑誌論文 |
| 出版者 |
The Pharmaceutical Society of Japan
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| 発行日 | 2017-03-01 |
| 権利情報 |
© 2017 The Pharmaceutical Society of Japan
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| 出版タイプ | Version of Record（出版社版。早期公開を含む） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 0918-6158
[ISSN] 1347-5215
[NCID] AA10885497
[DOI] 10.1248/bpb.b16-00784
[DOI] https://doi.org/10.1248/bpb.b16-00784
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