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.
Highlights
IntroductionThe prognosis for patients with brain ischemia remains poor
Despite decades of research, the prognosis for patients with brain ischemia remains poor
In this paper using different approaches, we demonstrated that i) mapacalcine is able to inhibit cell calcium influx in mouse cortical embryonic neurons under different conditions occurring during stroke, ii) the target of mapacalcine is, at least in part, a subtype of L-type calcium channel and mapacalcine binds only to channels in an opened state iii) neuron survival after Oxygen Glucose Deprivation (OGD) is enhanced when cells are treated with mapacalcine before or after OGD
Summary
The prognosis for patients with brain ischemia remains poor. Brain cells suffer from oxygen and glucose deprivation (OGD) This results in a dramatic neuronal depolarization, release of excitatory neurotransmitters, and reduced neurotransmitter re-uptake from the synaptic space. Specific receptors for this protein have been detected in various tissues: intestinal smooth muscle, brain, kidney, and liver [16,17,18,19,20] Among these studies, those conducted on cultured hepatocytes, demonstrated that mapacalcine was able to completely inhibit a calcium influx triggered by ischemia/reperfusion without affecting cell viability [17]. Statistical analyses of cell viability and LDH results were assessed using one factor ANOVA test following by post-hoc test (P,0.05)
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