Document Detail


Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis.
MedLine Citation:
PMID:  16497104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepcidin, a key regulator of iron metabolism, decreases intestinal absorption of iron and its release from macrophages. Iron, anemia, hypoxia, and inflammation were reported to influence hepcidin expression. To investigate regulation of the expression of hepcidin and other iron-related genes, we manipulated erythropoietic activity in mice. Erythropoiesis was inhibited by irradiation or posttransfusion polycythemia and stimulated by phenylhydrazine administration and erythropoietin. Gene expression of hepcidin and other iron-related genes (hemojuvelin, DMT1, ferroportin, transferrin receptors, ferritin) in the liver was measured by the real-time polymerase chain reaction. Hepcidin expression increased despite severe anemia when hematopoiesis was inhibited by irradiation. Suppression of erythropoiesis by posttransfusion polycythemia or irradiation also increased hepcidin mRNA levels. Compensated hemolysis induced by repeated phenylhydrazine administration did not change hepcidin expression. The decrease caused by exogenous erythropoeitin was blocked by postirradiation bone marrow suppression. The hemolysis and anemia decrease hepcidin expression only when erythropoiesis is functional; on the other hand, if erythropoiesis is blocked, even severe anemia does not lead to a decrease of hepcidin expression, which is indeed increased. We propose that hepcidin is exclusively sensitive to iron utilization for erythropoiesis and hepatocyte iron balance, and these changes are not sensed by other genes involved in the control of iron metabolism in the liver.
Authors:
M Vokurka; J Krijt; K Sulc; E Necas
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  55     ISSN:  0862-8408     ISO Abbreviation:  Physiol Res     Publication Date:  2006  
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-02-15     Revised Date:  2008-04-02    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  667-74     Citation Subset:  IM    
Affiliation:
Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic. mvoku@LF1.cuni.cz
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MeSH Terms
Descriptor/Qualifier:
Anemia, Hemolytic / chemically induced,  metabolism,  physiopathology
Animals
Antimicrobial Cationic Peptides / metabolism*
Cation Transport Proteins / metabolism
Erythropoiesis* / drug effects,  radiation effects
Erythropoietin / pharmacology
Ferritins / metabolism
Gamma Rays
Gene Expression Regulation
Hemolysis* / drug effects,  radiation effects
Iron Compounds / metabolism
Liver / drug effects,  metabolism*,  radiation effects
Male
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL
Phenylhydrazines
Polycythemia / metabolism,  physiopathology
RNA, Messenger / metabolism*
Receptors, Transferrin / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Cation Transport Proteins; 0/Hfe2 protein, mouse; 0/Iron Compounds; 0/Membrane Proteins; 0/Phenylhydrazines; 0/RNA, Messenger; 0/Receptors, Transferrin; 0/hepcidin; 0/metal transporting protein 1; 0/solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2; 100-63-0/phenylhydrazine; 11096-26-7/Erythropoietin; 9007-73-2/Ferritins

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