BiopestPeptidV1, Main, Exploration, bibRecord, 000785

Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.

Identifieur interne : 000785 ( Main/Exploration ); précédent : 000784; suivant : 000786

Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.

Auteurs : C. Castillo [Chili] ; S. Zaror [Chili] ; M. Gonzalez [Chili] ; A. Hidalgo [Chili] ; C F Burgos [Chili] ; O I Cabezas [Chili] ; F. Hugues [Chili] ; S P Jiménez [Chili] ; E. González-Horta [Chili] ; I. González-Chavarría [Chili] ; J. Gavilán [Chili] ; R. Montesino [Chili] ; O. Sánchez [Chili] ; Manuela G. Lopez [Espagne] ; J. Fuentealba [Chili] ; J R Toledo [Chili]

Source :

Redox biology [ 2213-2317 ] ; 2018.

RBID : pubmed:28987867

Descripteurs français

KwdFr :
- Animaux (MeSH), Cellules CHO (MeSH), Cellules PC12 (MeSH), Cricetulus (MeSH), Humains (MeSH), Neurones (cytologie), Neurones (effets des médicaments et des substances chimiques), Neurones (métabolisme), Neuroprotecteurs (métabolisme), Neuroprotecteurs (pharmacologie), Protéines recombinantes (génétique), Protéines recombinantes (pharmacologie), Rats (MeSH), Récepteur érythropoïétine (métabolisme), Stress oxydatif (effets des médicaments et des substances chimiques), Survie cellulaire (effets des médicaments et des substances chimiques), Érythropoïétine (génétique), Érythropoïétine (pharmacologie).
MESH :
- cytologie : Neurones.
- effets des médicaments et des substances chimiques : Neurones, Stress oxydatif, Survie cellulaire.
- génétique : Protéines recombinantes, Érythropoïétine.
- métabolisme : Neurones, Neuroprotecteurs, Récepteur érythropoïétine.
- pharmacologie : Neuroprotecteurs, Protéines recombinantes, Érythropoïétine.
- Animaux, Cellules CHO, Cellules PC12, Cricetulus, Humains, Rats.

English descriptors

KwdEn :
- Animals (MeSH), CHO Cells (MeSH), Cell Survival (drug effects), Cricetulus (MeSH), Erythropoietin (genetics), Erythropoietin (pharmacology), Humans (MeSH), Neurons (cytology), Neurons (drug effects), Neurons (metabolism), Neuroprotective Agents (metabolism), Neuroprotective Agents (pharmacology), Oxidative Stress (drug effects), PC12 Cells (MeSH), Rats (MeSH), Receptors, Erythropoietin (metabolism), Recombinant Proteins (genetics), Recombinant Proteins (pharmacology).
MESH :
- chemical , genetics : Erythropoietin, Recombinant Proteins.
- cytology : Neurons.
- drug effects : Cell Survival, Neurons, Oxidative Stress.
- metabolism : Neurons, Neuroprotective Agents, Receptors, Erythropoietin.
- chemical , pharmacology : Erythropoietin, Neuroprotective Agents, Recombinant Proteins.
- Animals, CHO Cells, Cricetulus, Humans, PC12 Cells, Rats.

Abstract

Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR), it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL) was purified from skimmed goat milk. Recombinant human erythropoietin (Epo) was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1h with EpoL or Epo and exposed to oxidative agents (H₂O₂ or FCCP); cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15min of oxygen and glucose deprivation (OGD) and the neuroprotective drugs EpoL or Epo were incubated for 2h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases.

DOI: 10.1016/j.redox.2017.09.010
PubMed: 28987867
PubMed Central: PMC5975214

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000A96
to stream Main, to step Curation: 000A96

Le document en format XML

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<author><name sortKey="Jimenez, S P" sort="Jimenez, S P" uniqKey="Jimenez S" first="S P" last="Jiménez">S P Jiménez</name>
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<country xml:lang="fr">Chili</country>
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<author><name sortKey="Gonzalez Horta, E" sort="Gonzalez Horta, E" uniqKey="Gonzalez Horta E" first="E" last="González-Horta">E. González-Horta</name>
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<country xml:lang="fr">Chili</country>
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<author><name sortKey="Gonzalez Chavarria, I" sort="Gonzalez Chavarria, I" uniqKey="Gonzalez Chavarria I" first="I" last="González-Chavarría">I. González-Chavarría</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
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<author><name sortKey="Gavilan, J" sort="Gavilan, J" uniqKey="Gavilan J" first="J" last="Gavilán">J. Gavilán</name>
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<country xml:lang="fr">Chili</country>
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<author><name sortKey="Montesino, R" sort="Montesino, R" uniqKey="Montesino R" first="R" last="Montesino">R. Montesino</name>
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<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
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<author><name sortKey="Sanchez, O" sort="Sanchez, O" uniqKey="Sanchez O" first="O" last="Sánchez">O. Sánchez</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
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<author><name sortKey="Lopez, Manuela G" sort="Lopez, Manuela G" uniqKey="Lopez M" first="Manuela G" last="Lopez">Manuela G. Lopez</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology and Therapeutics, "Instituo Teófilo Hernando", Universidad Autónoma de Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Pharmacology and Therapeutics, "Instituo Teófilo Hernando", Universidad Autónoma de Madrid</wicri:regionArea>
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<country xml:lang="fr">Chili</country>
<wicri:regionArea>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
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<author><name sortKey="Toledo, J R" sort="Toledo, J R" uniqKey="Toledo J" first="J R" last="Toledo">J R Toledo</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile. Electronic address: jotoledo@udec.cl.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.</title>
<author><name sortKey="Castillo, C" sort="Castillo, C" uniqKey="Castillo C" first="C" last="Castillo">C. Castillo</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zaror, S" sort="Zaror, S" uniqKey="Zaror S" first="S" last="Zaror">S. Zaror</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gonzalez, M" sort="Gonzalez, M" uniqKey="Gonzalez M" first="M" last="Gonzalez">M. Gonzalez</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hidalgo, A" sort="Hidalgo, A" uniqKey="Hidalgo A" first="A" last="Hidalgo">A. Hidalgo</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Burgos, C F" sort="Burgos, C F" uniqKey="Burgos C" first="C F" last="Burgos">C F Burgos</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cabezas, O I" sort="Cabezas, O I" uniqKey="Cabezas O" first="O I" last="Cabezas">O I Cabezas</name>
<affiliation wicri:level="1"><nlm:affiliation>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan</wicri:regionArea>
<wicri:noRegion>Chillan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hugues, F" sort="Hugues, F" uniqKey="Hugues F" first="F" last="Hugues">F. Hugues</name>
<affiliation wicri:level="1"><nlm:affiliation>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan</wicri:regionArea>
<wicri:noRegion>Chillan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jimenez, S P" sort="Jimenez, S P" uniqKey="Jimenez S" first="S P" last="Jiménez">S P Jiménez</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gonzalez Horta, E" sort="Gonzalez Horta, E" uniqKey="Gonzalez Horta E" first="E" last="González-Horta">E. González-Horta</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gonzalez Chavarria, I" sort="Gonzalez Chavarria, I" uniqKey="Gonzalez Chavarria I" first="I" last="González-Chavarría">I. González-Chavarría</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gavilan, J" sort="Gavilan, J" uniqKey="Gavilan J" first="J" last="Gavilán">J. Gavilán</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Montesino, R" sort="Montesino, R" uniqKey="Montesino R" first="R" last="Montesino">R. Montesino</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
<wicri:noRegion>Concepción</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sanchez, O" sort="Sanchez, O" uniqKey="Sanchez O" first="O" last="Sánchez">O. Sánchez</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
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<affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology and Therapeutics, "Instituo Teófilo Hernando", Universidad Autónoma de Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
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<author><name sortKey="Toledo, J R" sort="Toledo, J R" uniqKey="Toledo J" first="J R" last="Toledo">J R Toledo</name>
<affiliation wicri:level="1"><nlm:affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile. Electronic address: jotoledo@udec.cl.</nlm:affiliation>
<country xml:lang="fr">Chili</country>
<wicri:regionArea>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción</wicri:regionArea>
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<series><title level="j">Redox biology</title>
<idno type="eISSN">2213-2317</idno>
<imprint><date when="2018" type="published">2018</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>CHO Cells (MeSH)</term>
<term>Cell Survival (drug effects)</term>
<term>Cricetulus (MeSH)</term>
<term>Erythropoietin (genetics)</term>
<term>Erythropoietin (pharmacology)</term>
<term>Humans (MeSH)</term>
<term>Neurons (cytology)</term>
<term>Neurons (drug effects)</term>
<term>Neurons (metabolism)</term>
<term>Neuroprotective Agents (metabolism)</term>
<term>Neuroprotective Agents (pharmacology)</term>
<term>Oxidative Stress (drug effects)</term>
<term>PC12 Cells (MeSH)</term>
<term>Rats (MeSH)</term>
<term>Receptors, Erythropoietin (metabolism)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Cellules CHO (MeSH)</term>
<term>Cellules PC12 (MeSH)</term>
<term>Cricetulus (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Neurones (cytologie)</term>
<term>Neurones (effets des médicaments et des substances chimiques)</term>
<term>Neurones (métabolisme)</term>
<term>Neuroprotecteurs (métabolisme)</term>
<term>Neuroprotecteurs (pharmacologie)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (pharmacologie)</term>
<term>Rats (MeSH)</term>
<term>Récepteur érythropoïétine (métabolisme)</term>
<term>Stress oxydatif (effets des médicaments et des substances chimiques)</term>
<term>Survie cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Érythropoïétine (génétique)</term>
<term>Érythropoïétine (pharmacologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Erythropoietin</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Neurones</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Neurons</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term>
<term>Neurons</term>
<term>Oxidative Stress</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Neurones</term>
<term>Stress oxydatif</term>
<term>Survie cellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines recombinantes</term>
<term>Érythropoïétine</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term>
<term>Neuroprotective Agents</term>
<term>Receptors, Erythropoietin</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Neurones</term>
<term>Neuroprotecteurs</term>
<term>Récepteur érythropoïétine</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Neuroprotecteurs</term>
<term>Protéines recombinantes</term>
<term>Érythropoïétine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Erythropoietin</term>
<term>Neuroprotective Agents</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>CHO Cells</term>
<term>Cricetulus</term>
<term>Humans</term>
<term>PC12 Cells</term>
<term>Rats</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules CHO</term>
<term>Cellules PC12</term>
<term>Cricetulus</term>
<term>Humains</term>
<term>Rats</term>
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<front><div type="abstract" xml:lang="en">Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR), it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL) was purified from skimmed goat milk. Recombinant human erythropoietin (Epo) was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1h with EpoL or Epo and exposed to oxidative agents (H<sub>2</sub>
O<sub>2</sub>
 or FCCP); cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15min of oxygen and glucose deprivation (OGD) and the neuroprotective drugs EpoL or Epo were incubated for 2h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases.</div>
</front>
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<DateCompleted><Year>2018</Year>
<Month>07</Month>
<Day>11</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2213-2317</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>14</Volume>
<PubDate><Year>2018</Year>
<Month>04</Month>
</PubDate>
</JournalIssue>
<Title>Redox biology</Title>
<ISOAbbreviation>Redox Biol</ISOAbbreviation>
</Journal>
<ArticleTitle>Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.</ArticleTitle>
<Pagination><MedlinePgn>285-294</MedlinePgn>
</Pagination>
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<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.redox.2017.09.010</ELocationID>
<Abstract><AbstractText>Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR), it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL) was purified from skimmed goat milk. Recombinant human erythropoietin (Epo) was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1h with EpoL or Epo and exposed to oxidative agents (H<sub>2</sub>
O<sub>2</sub>
 or FCCP); cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15min of oxygen and glucose deprivation (OGD) and the neuroprotective drugs EpoL or Epo were incubated for 2h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases.</AbstractText>
<CopyrightInformation>Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Castillo</LastName>
<ForeName>C</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zaror</LastName>
<ForeName>S</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gonzalez</LastName>
<ForeName>M</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
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<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
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<ForeName>C F</ForeName>
<Initials>CF</Initials>
<AffiliationInfo><Affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cabezas</LastName>
<ForeName>O I</ForeName>
<Initials>OI</Initials>
<AffiliationInfo><Affiliation>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hugues</LastName>
<ForeName>F</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Clinical Sciences Department, School of Veterinary Sciences, Universidad de Concepción, Avenida Vicente Méndez 595, Chillan, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiménez</LastName>
<ForeName>S P</ForeName>
<Initials>SP</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>González-Horta</LastName>
<ForeName>E</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>González-Chavarría</LastName>
<ForeName>I</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Gavilán</LastName>
<ForeName>J</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
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<Author ValidYN="Y"><LastName>Montesino</LastName>
<ForeName>R</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Sánchez</LastName>
<ForeName>O</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lopez</LastName>
<ForeName>Manuela G</ForeName>
<Initials>MG</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Therapeutics, "Instituo Teófilo Hernando", Universidad Autónoma de Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fuentealba</LastName>
<ForeName>J</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Laboratory of Screening of Neuroactive Compound, Physiology Department. School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Toledo</LastName>
<ForeName>J R</ForeName>
<Initials>JR</Initials>
<AffiliationInfo><Affiliation>Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción, Chile. Electronic address: jotoledo@udec.cl.</Affiliation>
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<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>09</Month>
<Day>21</Day>
</ArticleDate>
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<ISSNLinking>2213-2317</ISSNLinking>
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Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.

Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.

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