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Cystathionine β-synthase is required for body iron homeostasis.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2018 Jan; Vol. 67 (1), pp. 21-35. - Publication Year :
- 2018
-
Abstract
- Cystathionine β-synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin-6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS <superscript>-/-</superscript> ) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis-like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin-6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2-related factor-2 and an up-regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS-overexpressing adenovirus into CBS mutant mice could partially reverse the iron-related phenotype.<br />Conclusion: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis-like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (Hepatology 2018;67:21-35).<br /> (© 2017 by the American Association for the Study of Liver Diseases.)
- Subjects :
- Anemia, Iron-Deficiency metabolism
Animals
Biopsy, Needle
Blotting, Western
Cells, Cultured
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Hepatocytes metabolism
Hepcidins metabolism
Homeostasis
Humans
Immunohistochemistry
Liver metabolism
Liver pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Multivariate Analysis
Random Allocation
Real-Time Polymerase Chain Reaction methods
Reference Values
Anemia, Iron-Deficiency enzymology
Anemia, Iron-Deficiency pathology
Cystathionine beta-Synthase metabolism
Hepatocytes enzymology
Iron metabolism
Liver enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 67
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 28859237
- Full Text :
- https://doi.org/10.1002/hep.29499