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Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways
Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often con...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522880/ https://www.ncbi.nlm.nih.gov/pubmed/23259053 http://dx.doi.org/10.1242/bio.20122170 |
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author | Hanana, Houda Talarmin, Hélène Pennec, Jean-Pierre Droguet, Mickael Morel, Julie Dorange, Germaine |
author_facet | Hanana, Houda Talarmin, Hélène Pennec, Jean-Pierre Droguet, Mickael Morel, Julie Dorange, Germaine |
author_sort | Hanana, Houda |
collection | PubMed |
description | Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA. |
format | Online Article Text |
id | pubmed-3522880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-35228802012-12-20 Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways Hanana, Houda Talarmin, Hélène Pennec, Jean-Pierre Droguet, Mickael Morel, Julie Dorange, Germaine Biol Open Research Article Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA. The Company of Biologists 2012-09-25 /pmc/articles/PMC3522880/ /pubmed/23259053 http://dx.doi.org/10.1242/bio.20122170 Text en © 2012. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Article Hanana, Houda Talarmin, Hélène Pennec, Jean-Pierre Droguet, Mickael Morel, Julie Dorange, Germaine Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title | Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title_full | Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title_fullStr | Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title_full_unstemmed | Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title_short | Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways |
title_sort | effect of okadaic acid on cultured clam heart cells: involvement of mapkinase pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522880/ https://www.ncbi.nlm.nih.gov/pubmed/23259053 http://dx.doi.org/10.1242/bio.20122170 |
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