Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload

• Published in: PloS one 2013-07, Vol.8 (7), p.e66194-e66194
• Main Authors: Moha Ou Maati, Hamid, Widmann, Catherine, Sedjelmaci, Djamila, Gallois, Djamila Sedjelmaci Bernard, Gallois, Bernard, Heurteaux, Catherine, Borsotto, Marc, Hugues, Michel
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biology; Blocking; Brain; Brain research; Calcium; Calcium - metabolism; Calcium Channel Blockers - isolation & purification; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium channels (L-type); Calcium channels (R-type); Calcium channels (voltage-gated); Calcium Channels, L-Type - metabolism; Cell Hypoxia; Cell survival; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Channels; Deprivation; Drug therapy; Embryo, Mammalian; Experiments; Fibrinolysis; Genetic aspects; Glucose; Glucose - deficiency; Glutamic acid receptors (ionotropic); HEK293 Cells; Humans; Hypoxia; Ischemia; Laboratory animals; Male; Medical prognosis; Medicine; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; N-Methyl-D-aspartic acid receptors; Nervous system; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oxygen; Oxygen - metabolism; Oxygen - pharmacology; Pain; Patch-Clamp Techniques; Peptides; Physiological aspects; Porifera - chemistry; Primary Cell Culture; Protection and preservation; Proteins - isolation & purification; Proteins - pharmacology; Receptors; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Rodents; Stroke; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066194

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.