| First Author | Darshan D | Year | 2009 |
| Journal | Hepatology | Volume | 50 |
| Issue | 3 | Pages | 852-60 |
| PubMed ID | 19492434 | Mgi Jnum | J:166515 |
| Mgi Id | MGI:4847968 | Doi | 10.1002/hep.23058 |
| Citation | Darshan D, et al. (2009) Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage. Hepatology 50(3):852-60 |
| abstractText | Ferritin plays a central role in iron metabolism by acting both as iron storage and a detoxifying protein. We generated a ferritin H allele with loxP sites and studied the conditional ferritin H deletion in adult mice. Ten days after Mx-Cre induced deletion, ferritin H messenger RNA (mRNA) was below 5% in the liver, spleen, and bone marrow of deleted mice compared to control littermates. Mice lost their cellular iron stores indicating the requirement of ferritin H in iron deposition. Serum iron and transferrin saturation were slightly increased and correlated with a two-fold increased liver hepcidin 1 mRNA and a reduced duodenal DcytB mRNA level. Under a normal iron regimen, deleted mice survived for 2 years without visible disadvantage. Mice fed on a high iron diet prior to ferritin H deletion suffered from severe liver damage. Similarly, ferritin H deleted mouse embryonic fibroblasts showed rapid cell death after exposure to iron salt in the medium. This was reversed by wild-type ferritin H but not by a ferritin H mutant lacking ferroxidase activity. Cell death was preceded by an increase in cytoplasmic free iron, reactive oxygen species, and mitochondrial depolarization. Conclusion: Our results provide evidence that the iron storage function of ferritin plays a major role in preventing iron-mediated cell and tissue damage. |
