ArticleBrain research2010
Erythropoietin-induced neuroprotection requires cystine glutamate exchanger activity.
Article in Brain research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Does erythropoietin affect the outcome and complication rates of patient with traumatic brain injury? A pooled-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Pooled it
- Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- Whether Erythropoietin can be a Neuroprotective Agent against Premature Brain Injury: Cellular Mechanisms and Clinical Efficacy.Current neuropharmacology · 2022Review
- Protective effects of erythropoietin against cuprizone-induced oxidative stress and demyelination in the mouse corpus callosum.Iranian journal of basic medical sciences · 2017Article
- Age-associated expression of erythropoietin and its receptor in rat spiral ganglion neurons and its association with neuronal apoptosis and hearing alterations.Molecular medicine reports · 2017Article
- Signal transducer and activator of transcription 3 and 5 regulate system Xc- and redox balance in human breast cancer cells.Molecular and cellular biochemistry · 2015Article
- Regulation of System xc(-) by Pharmacological Manipulation of Cellular Thiols.Oxidative medicine and cellular longevity · 2015Article
- Phosphoinositide 3-kinases upregulate system xc(-) via eukaryotic initiation factor 2α and activating transcription factor 4 - A pathway active in glioblastomas and epilepsy.Antioxidants & redox signaling · 2014Article
- Long-term moderate dose exogenous erythropoietin treatment protects from intermittent hypoxia-induced spatial learning deficits and hippocampal oxidative stress in young rats.Neurochemical research · 2014Article
- The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities.Antioxidants & redox signaling · 2013Review
- Trpc2 depletion protects red blood cells from oxidative stress-induced hemolysis.Experimental hematology · 2012Article
- The transient receptor potential (TRP) channel TRPC3 TRP domain and AMP-activated protein kinase binding site are required for TRPC3 activation by erythropoietin.The Journal of biological chemistry · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Erythropoietin (Epo) has been used for many years in neonates for the treatment of anemia of prematurity. Epo has also been proposed for treatment of neonatal brain injury, as mounting evidence suggests neuroprotective properties for Epo. However, Epo's neuroprotective mechanism of action is poorly understood. In this study we hypothesized that Epo may confer neuroprotection by enhancing cellular redox defense brought about by cellular glutathione (GSH). This was examined in cultures of differentiated cortical neural stem cells and using the B104 cell line as model systems. Our data shows that Epo causes a time- and dose-dependent increase in expression and activity of system Xc(-), the transporter responsible for uptake of cystine for the production of glutathione. Cystine uptake increases 3-5 fold in differentiated neural stem cells and B104 cells treated with Epo. Exposure of cells to 100 microM kainate suppressed cellular GSH and caused excitotoxicity, but GSH levels and cell viability were completely restored by Epo in the continued presence of kainate. This rescue effect of Epo vanished if system Xc(-) was inhibited pharmacologically using S4-CPG in the presence of Epo leading to marked cell death of B104 cells and cultured mouse cortical neural stem cells. This could also be achieved using xCT siRNA to decrease xCT expression. This data suggests that system Xc(-) activity and protein expression are positively regulated by Epo directly explaining its neuroprotective effect.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.