General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain
Tomoharu Tanaka,Shinichi Kai,Tomohiro Koyama,Hiroki Daijo,Takehiko Adachi,Kazuhiko Fukuda,Kiichi Hirota +6 more
TL;DR: The 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.
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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 (010–10%) 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
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