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ID 47060
本文ファイル
著者
Ishida, Keishi
Kotake, Yaichiro 大学院医歯薬保健学研究科(薬) 広大研究者総覧
Sanoh, Seigo 大学院医歯薬保健学研究科(薬) 広大研究者総覧
Ohta, Shigeru 大学院医歯薬保健学研究科(薬)
キーワード
lead
glutamate receptor 2
neurotoxicity
mitogen-activated protein kinase (MAPK)
NDC
医学
抄録(英)
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.
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.).
掲載誌名
Biological and Pharmaceutical Bulletin
40巻
3号
開始ページ
303
終了ページ
309
出版年月日
2017-03-01
出版者
The Pharmaceutical Society of Japan
ISSN
0918-6158
1347-5215
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
publisher
権利情報
© 2017 The Pharmaceutical Society of Japan
関連情報URL
部局名
医歯薬保健学研究科