Deletion of hephaestin and ceruloplasmin induces a serious systemic iron deficiency and disrupts iron homeostasis
Journal Article
·
· Biochemical and Biophysical Research Communications
- Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University (China)
Highlights: • Heph/Cp double knockout mice. • Systemic iron deficiency. • Local tissue iron overload. Multi-copper ferroxidases (MCFs) play important roles in cellular iron metabolism and homeostasis. In this study, we generated the hephaestin (Heph), ceruloplasmin (Cp) single and Heph/Cp double knockout (KO) mice to investigate the roles of MCFs in iron transport among system and vital organs in mice at 4 weeks and 6 months of age. Compared with wild-type (WT) mice, Heph/Cp mice at both ages presented with severe anemia and significantly lower iron level in the serum and spleen, but with significantly higher iron level in the liver, heart, kidney, and duodenal enterocytes. Furthermore, Heph/Cp mice displayed significantly lower level of hepcidin mRNA and transferrin receptor 1 (TFR1) protein expression, but significantly higher level of ferroportin 1 (FPN1) protein expression in the liver than WT mice at 6 months of age. Liver superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were significantly lower in Heph/Cp KO mice than WT mice at 6 months of age. Together, our results suggest that ablation of HEPH and CP could lead to severe systemic iron deficiency and local tissue iron overload, which disrupt the whole body iron homeostasis and impact on tissue functions.
- OSTI ID:
- 23105583
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study
Interplay of adipocyte and hepatocyte: Leptin upregulates hepcidin
Retinoic acid modulates iron metabolism imbalance in anemia of inflammation induced by LPS via reversely regulating hepcidin and ferroportin expression
Journal Article
·
Fri Sep 09 00:00:00 EDT 2016
· Biochemical and Biophysical Research Communications
·
OSTI ID:22606206
Interplay of adipocyte and hepatocyte: Leptin upregulates hepcidin
Journal Article
·
Sun Jan 14 23:00:00 EST 2018
· Biochemical and Biophysical Research Communications
·
OSTI ID:23134416
Retinoic acid modulates iron metabolism imbalance in anemia of inflammation induced by LPS via reversely regulating hepcidin and ferroportin expression
Journal Article
·
Fri Dec 14 23:00:00 EST 2018
· Biochemical and Biophysical Research Communications
·
OSTI ID:23107885