title: Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.
abstract: 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.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (UMR7275), Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Moha Ou Maati
authors.forename: Catherine
authors.initials: C
authors.lastname: Widmann
authors.forename: Djamila
authors.initials: D
authors.lastname: Sedjelmaci
authors.forename: Djamila Sedjelmaci Bernard
authors.initials: DS
authors.lastname: Gallois
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallois
authors.forename: Djamila Sedjelmaci Bernard
authors.initials: DS
authors.lastname: Gallois
authors.forename: Catherine
authors.initials: C
authors.lastname: Heurteaux
authors.forename: Marc
authors.initials: M
authors.lastname: Borsotto
authors.forename: Michel
authors.initials: M
authors.lastname: Hugues
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004622:Embryo, Mammalian; D005947:Glucose / Q000172:deficiency; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011161:Porifera / Q000737:chemistry; D061251:Primary Cell Culture; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011506:Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C106560:mapacalcine; D005947:Glucose; D010100:Oxygen; D002118:Calcium