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Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes
Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we r...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585279/ https://www.ncbi.nlm.nih.gov/pubmed/23469098 http://dx.doi.org/10.1371/journal.pone.0057898 |
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author | Noguchi, Yusuke Shinozaki, Youichi Fujishita, Kayoko Shibata, Keisuke Imura, Yoshio Morizawa, Yosuke Gachet, Christian Koizumi, Schuichi |
author_facet | Noguchi, Yusuke Shinozaki, Youichi Fujishita, Kayoko Shibata, Keisuke Imura, Yoshio Morizawa, Yosuke Gachet, Christian Koizumi, Schuichi |
author_sort | Noguchi, Yusuke |
collection | PubMed |
description | Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y(1) receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y(1) receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y(1) receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y(1) receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A(1) receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y(1) receptors to upregulate IL-6, thereby leading to A(1) receptor-mediated neuro-protection against MeHg. |
format | Online Article Text |
id | pubmed-3585279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35852792013-03-06 Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes Noguchi, Yusuke Shinozaki, Youichi Fujishita, Kayoko Shibata, Keisuke Imura, Yoshio Morizawa, Yosuke Gachet, Christian Koizumi, Schuichi PLoS One Research Article Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y(1) receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y(1) receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y(1) receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y(1) receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A(1) receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y(1) receptors to upregulate IL-6, thereby leading to A(1) receptor-mediated neuro-protection against MeHg. Public Library of Science 2013-02-28 /pmc/articles/PMC3585279/ /pubmed/23469098 http://dx.doi.org/10.1371/journal.pone.0057898 Text en © 2013 Noguchi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Noguchi, Yusuke Shinozaki, Youichi Fujishita, Kayoko Shibata, Keisuke Imura, Yoshio Morizawa, Yosuke Gachet, Christian Koizumi, Schuichi Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title | Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title_full | Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title_fullStr | Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title_full_unstemmed | Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title_short | Astrocytes Protect Neurons against Methylmercury via ATP/P2Y(1) Receptor-Mediated Pathways in Astrocytes |
title_sort | astrocytes protect neurons against methylmercury via atp/p2y(1) receptor-mediated pathways in astrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585279/ https://www.ncbi.nlm.nih.gov/pubmed/23469098 http://dx.doi.org/10.1371/journal.pone.0057898 |
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