Cystathionine β-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter.

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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Zhao P,Qian C,Chen YJ,Sheng Y,Ke Y,Qian ZM

doi

10.1038/s41419-019-1951-0

subject

Has Abstract

pub_date

2019-09-24 00:00:00

pages

708

issue

10

issn

2041-4889

pii

10.1038/s41419-019-1951-0

journal_volume

10

pub_type

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