Cystathionine ß-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter.
Cell Death Dis
; 10(10): 708, 2019 09 24.
Article
em En
| MEDLINE
| ID: mdl-31551410
ABSTRACT
The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, including; two key enzymes involved in the heme biosynthetic pathway, ALAS2 (delta-aminolevulinate synthase 2) and FECH (ferrochelatase), a heme exporter from the cytosol and mitochondria, FLVCR (feline leukemia virus subgroup C cellular receptor) as well as EPO (erythropoietin), EPOR (erythropoietin receptor) and HIF-2α (hypoxia inducible factor-2 subunit α), in the blood, bone marrow or liver of CBS-/- (homozygous), CBS+/- (heterozygous) and CBS+/+ (Wild Type) mice. Our findings demonstrate that CBS deficiency can induce a significant reduction in the expression of ALAS2, FECH, FLVCR, HIF-2α, EPO, and EPOR as well as an increase in interleukin-6 (IL-6), hepcidin and iron content in the blood, bone marrow or liver of mice. We conclude that the suppression of erythropoiesis is mainly due to the CBS deficiency-induced disruption in the expression of heme biosynthetic enzymes and heme-transporter.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cistationina beta-Sintase
/
Heme
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China