Artículo
Convulsive Stress Mimics Brain Hypoxia and Promotes the P-Glycoprotein (P-gp) and Erythropoietin Receptor Overexpression. Recombinant Human Erythropoietin Effect on P-gp Activity
Merelli, Amalia Margarita; Ramos, Alberto Javier
; Lazarowski, Alberto Jorge; Auzmendi, Jerónimo Andrés
![Icon](/themes/CONICETDigital/images/conicet.png)
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
07/2019
Editorial:
Frontiers Media S.A.
Revista:
Frontiers in Neuroscience
ISSN:
1662-453X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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 similar way as seen by Tariquidar, demonstrating for first time that rHu-EPO can inhibit the P-gp-dependent efflux activity. Taking together, these data suggest that stimulation of EPO depending signaling system could not only play a central role in brain cell protection, but this system could be a new tool for reverse the pharmacoresistant phenotype in refractory epilepsy as well as in other pharmacoresistant hypoxic brain diseases expressing P-gp.
Palabras clave:
EPILEPSY
,
EPO-R
,
HYPOXIA
,
P-GP
,
RHU-EPO
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Colecciones
Articulos(IBCN)
Articulos de INST.DE BIOLO.CEL.Y NEURCS."PROF.E.DE ROBERTIS"
Articulos de INST.DE BIOLO.CEL.Y NEURCS."PROF.E.DE ROBERTIS"
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Merelli, Amalia Margarita; Ramos, Alberto Javier; Lazarowski, Alberto Jorge; Auzmendi, Jerónimo Andrés; 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 Media S.A.; Frontiers in Neuroscience; 13; JUL; 7-2019; 1-11
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