| First Author | Lenartowicz M | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 6 | Pages | 1410-1421 |
| PubMed ID | 28219768 | Mgi Jnum | J:256261 |
| Mgi Id | MGI:6105883 | Doi | 10.1016/j.bbadis.2017.02.020 |
| Citation | Lenartowicz M, et al. (2017) Copper therapy reduces intravascular hemolysis and derepresses ferroportin in mice with mosaic mutation (Atp7a(mo-ms)): An implication for copper-mediated regulation of the Slc40a1 gene expression. Biochim Biophys Acta 1863(6):1410-1421 |
| abstractText | Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis. We thus aimed to check whether copper supplementation recovers mutants from hemolytic insult and rebalance systemic iron regulation. Copper supplementation of 14-day-old mosaic mutants resulted in the reestablishment of hematological status, attenuation of hepicidin and concomitant induction of the iron exporter ferroportin/Slc40a1 expression in the liver, down-regulated in untreated mutants. Interestingly, treatment of wild-type males with copper, induced hepcidin-independent up-regulation of ferroportin protein level in hepatic macrophages in both young and adult (6-month-old) animals. Stimulatory effect of copper on ferroportin mRNA and protein levels was confirmed in bone marrow-derived macrophages isolated from both wild-type and mosaic mutant males. Our study indicates that copper is an important player in the regulation of the Slc40a1 gene expression. |
