Interplay between endothelin and erythropoietin in astroglia : the role in protection against hypoxia

  • We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.

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Metadaten
Author:Richard SchäferORCiDGND, Lars Mueller, Reinhild Buecheler, Barbara Proksch, Matthias Schwab, Christoph H. Gleiter, Lusine Danielyan
URN:urn:nbn:de:hebis:30:3-370568
DOI:https://doi.org/10.3390/ijms15022858
ISSN:1422-0067
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24557580
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2014/06/19
Date of first Publication:2014/02/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/02/19
Tag:aging; astroglia; endothelin; endothelin receptor type A antagonist; erythropoietin; hypoxia; neuroprotection
Volume:15
Issue:2
Page Number:18
First Page:2858
Last Page:2875
Note:
© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
HeBIS-PPN:368446409
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0