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Title: General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain.
Authors: Tanaka, Tomoharu  kyouindb  KAKEN_id
Kai, Shinichi
Koyama, Tomohiro
Daijo, Hiroki  kyouindb  KAKEN_id
Adachi, Takehiko
Fukuda, Kazuhiko  kyouindb  KAKEN_id
Hirota, Kiichi
Author's alias: 田中, 具治
Issue Date: Dec-2011
Publisher: Public Library of Science
Journal title: PloS one
Volume: 6
Issue: 12
Thesis number: e29378
Abstract: [Background]: Erythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes. [Methodology/Principal Findings]: BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA. [Conclusions/Significance]: Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.
Rights: © 2011 Tanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pone.0029378
PubMed ID: 22216265
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