Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.

Stroke is one of a major cause of death and adult disability. Despite intense researches, treatment for stroke remains reduced to fibrinolysis, a technique useful for less than 10% of patients. Finding molecules able to treat or at least to decrease the deleterious consequences of stroke is an urgen...

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Main Authors: Hamid Moha Ou Maati, Catherine Widmann, Djamila Sedjelmaci, Bernard Gallois, Catherine Heurteaux, Marc Borsotto, Michel Hugues
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23843951/?tool=EBI
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author Hamid Moha Ou Maati
Catherine Widmann
Djamila Sedjelmaci
Bernard Gallois
Catherine Heurteaux
Marc Borsotto
Michel Hugues
author_facet Hamid Moha Ou Maati
Catherine Widmann
Djamila Sedjelmaci
Bernard Gallois
Catherine Heurteaux
Marc Borsotto
Michel Hugues
author_sort Hamid Moha Ou Maati
collection DOAJ
description Stroke is one of a major cause of death and adult disability. Despite intense researches, treatment for stroke remains reduced to fibrinolysis, a technique useful for less than 10% of patients. Finding molecules able to treat or at least to decrease the deleterious consequences of stroke is an urgent need. Here, we showed that mapacalcine, a homodimeric peptide purified from the marine sponge Cliona vastifica, is able to protect mouse cortical neurons against hypoxia. We have also identified a subtype of L-type calcium channel as a target for mapacalcine and we showed that the channel has to be open for mapacalcine binding. The two main L-type subunits at the brain level are CaV1.3 and CaV1.2 subunits but mapacalcine was unable to block these calcium channels.Mapacalcine did not interfere with N-, P/Q- and R-type calcium channels. The protective effect was studied by measuring internal calcium level variation triggered by Oxygen Glucose Deprivation protocol, which mimics stroke, or glutamate stimulation. We showed that NMDA/AMPA receptors are not involved in the mapacalcine protection. The protective effect was confirmed by measuring the cell survival rate after Oxygen Glucose Deprivation condition. Our data indicate that mapacalcine is a promising molecule for stroke treatment.
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spelling doaj.art-cb11dc94c9884aa9bd9f780fee077e0f2022-12-21T22:41:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6619410.1371/journal.pone.0066194Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.Hamid Moha Ou MaatiCatherine WidmannDjamila SedjelmaciBernard GalloisCatherine HeurteauxMarc BorsottoMichel HuguesStroke is one of a major cause of death and adult disability. Despite intense researches, treatment for stroke remains reduced to fibrinolysis, a technique useful for less than 10% of patients. Finding molecules able to treat or at least to decrease the deleterious consequences of stroke is an urgent need. Here, we showed that mapacalcine, a homodimeric peptide purified from the marine sponge Cliona vastifica, is able to protect mouse cortical neurons against hypoxia. We have also identified a subtype of L-type calcium channel as a target for mapacalcine and we showed that the channel has to be open for mapacalcine binding. The two main L-type subunits at the brain level are CaV1.3 and CaV1.2 subunits but mapacalcine was unable to block these calcium channels.Mapacalcine did not interfere with N-, P/Q- and R-type calcium channels. The protective effect was studied by measuring internal calcium level variation triggered by Oxygen Glucose Deprivation protocol, which mimics stroke, or glutamate stimulation. We showed that NMDA/AMPA receptors are not involved in the mapacalcine protection. The protective effect was confirmed by measuring the cell survival rate after Oxygen Glucose Deprivation condition. Our data indicate that mapacalcine is a promising molecule for stroke treatment.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23843951/?tool=EBI
spellingShingle Hamid Moha Ou Maati
Catherine Widmann
Djamila Sedjelmaci
Bernard Gallois
Catherine Heurteaux
Marc Borsotto
Michel Hugues
Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
PLoS ONE
title Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
title_full Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
title_fullStr Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
title_full_unstemmed Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
title_short Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
title_sort mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23843951/?tool=EBI
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AT catherineheurteaux mapacalcineprotectsmouseneuronsagainsthypoxiabyblockingcellcalciumoverload
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