Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons
Biological and Pharmaceutical Bulletin Volume 40 Issue 3
Page 303-309
published_at 2017-03-01
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Title ( eng ) |
Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons
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Creator |
Ishida Keishi
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Source Title |
Biological and Pharmaceutical Bulletin
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Volume | 40 |
Issue | 3 |
Start Page | 303 |
End Page | 309 |
Abstract |
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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Keywords |
lead
glutamate receptor 2
neurotoxicity
mitogen-activated protein kinase (MAPK)
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Descriptions |
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 |
Medical sciences [ 490 ]
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Language |
eng
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Resource Type | journal article |
Publisher |
The Pharmaceutical Society of Japan
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Date of Issued | 2017-03-01 |
Rights |
© 2017 The Pharmaceutical Society of Japan
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Publish Type | Version of Record |
Access Rights | open access |
Source Identifier |
[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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