Convulsive Stress Mimics Brain Hypoxia and Promotes the P-Glycoprotein (P-gp) and Erythropoietin Receptor Overexpression. Recombinant Human Erythropoietin Effect on P-gp Activity

Frontiers in Neuroscience
A MerelliJerónimo Auzmendi

Abstract

Erythropoietin (EPO) is not only a hormone that promotes erythropoiesis but also has a neuroprotective effect on neurons attributed to its known anti-apoptotic action. Previously, our group has demonstrated that recombinant-human EPO (rHu-EPO) can protect neurons and recovery motor activity in a chemical focal brain hypoxia model (Merelli et al., 2011). We and others also have reported that repetitive seizures can mimic a hypoxic- like condition by HIF-1α nuclear translocation and high neuronal expression P-gp. Here, we report that a single 20-min status epilepticus (SE) induces P-gp and EPO-R expression in cortical pyramidal neurons and only P-gp expression in astrocytes. In vitro, excitotoxic stress (300 μM glutamate, 5 min), can also induce the expression of EPO-R and P-gp simultaneously with both HIF-1α and NFkB nuclear translocation in primary cortical neurons. Primary astrocytes exposed to chemical hypoxia with CoCl2 (0.3 mM, 6 h) increased P-gp expression as well as an increased efflux of Rhodamine 123 (Rho123) that is a P-gp substrate. Tariquidar, a specific 3er generation P-gp-blocker was used as an efflux inhibitor control. Astrocytes treated with rHu-EPO showed a significant recovery of the Rho123 retention in a simi...Continue Reading

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Citations

Jan 17, 2020·Current Pharmaceutical Design·Mónica E Ureña-GuerreroCarlos Beas-Zárate
Apr 8, 2020·Frontiers in Behavioral Neuroscience·Jerónimo AuzmendiAlberto Lazarowski
Dec 17, 2020·Journal of Alzheimer's Disease : JAD·Amalia MerelliJerónimo Auzmendi
Apr 23, 2020·Pharmacology & Therapeutics·Eva Gil-MartinsRenata Silva

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Methods Mentioned

BETA
nuclear translocation
Fluorescence

Software Mentioned

Graph Pad prism
ImageJ

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