Endogenous nitric oxide attenuates erythropoietin gene expression in vivo

This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and kidneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS...

Full description

Saved in:
Bibliographic Details
Published in:Pflügers Archiv 2000-02, Vol.439 (4), p.445-448
Main Authors: Todorov, V, Gess, B, Gödecke, A, Wagner, C, Schräder, J, Kurtz, A
Format: Article
Language:English
Subjects:
Animals
DNA-Binding Proteins - genetics
Enzyme Inhibitors - pharmacology
Erythropoietin - genetics
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Enzymologic - physiology
Hypoxia
Hypoxia - physiopathology
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Kidney - enzymology
Liver - enzymology
Mice
Mice, Inbred C57BL
Mice, Knockout
NG-Nitroarginine Methyl Ester - pharmacology
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nuclear Proteins - genetics
RNA, Messenger - metabolism
Rodents
Transcription Factors - genetics
Transcriptional Activation
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and kidneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS) knockout mice (eNOS-/-), and wt treated with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (50 mg x kg(-1) x day(-1)) for 4 days (wt+L-NAME). EPO gene expression was stimulated by normobaric hypoxia (8% O2) or by 0.1% carbon monoxide (CO) inhalation for 4 h each, or by intraperitoneal injection of 60 mg/kg cobaltous chloride (CoCl2) for 6 h. Renal EPO mRNA in wt increased 12-, 40-, and 13-fold over normoxic levels in response to hypoxia, CO and CoCl2 respectively. EPO mRNA was detectable in the livers only after CO exposure. Renal and hepatic EPO gene expression in wt+L-NAME appeared moderately increased relative to wt with a maximal 2.5-fold enhancement after CO exposure. EPO mRNA levels in eNOS-/- mirrored those of wt+L-NAME, but the effects were less prominent. Our data suggest that endogenous NO attenuates EPO gene expression in mice. This effect is dependent on the rate of EPO gene induction.
ISSN:0031-6768
1432-2013
DOI:10.1007/s004249900192