Iron accumulation after SCI resulted in the upregulation of transferrin receptor (TfR) and divalent metal transporter1 (DMT1), which exacerbated the intracellular iron overload.
The involvement of iron responsive element (-) divalent metal transporter 1-mediated the spinal iron overload via CXCL10/CXCR3 pathway in neuropathic pain in rats.
While the divalent metal transporter 1 (DMT1) plays a well-established role in the absorption of dietary iron, up-regulation of intestinal DMT1 is associated with iron overload in both humans and rodents.
Tfr1, Dmt1, ferritin and ferroportin1 exist in bone tissue of rats, and they may be involved in the pathological process of iron overload-induced bone lesion.
These results suggest that the increased expression of DMT1 induces iron overload and iron overload induces osteoblast autophagy and apoptosis, thus affecting the pathological processes of osteoporosis.
Evidence proved that activation of NMDARs could promote iron overload and iron-induced neurotoxicity by enhancing iron importer divalent metal transporter 1 (DMT1)-mediated iron uptake and iron releasing from lysosome.
Treatment with LTCC, TTCC, DMT1 blockers, and DFO reduced cardiac iron deposit, cardiac malondialdehyde (MDA), plasma non-transferrin-bound iron, and improved heart rate variability and left ventricular (LV) function in thalassemic mice with iron overload.
Our data confirm the major role of DMT1 in the maintenance of iron homeostasis in humans and demonstrate that the N491S mutation, through its deleterious effect on protein trafficking, contributes together with the G212V mutation to the development of anemia and hepatic iron overload.
This activity may explain the distinguishing iron overload seen in this patient in addition to microcytic anemia that is absent in parallel rodent models of DMT1 deficiency.
We propose that DMT1(C1246T) (R416C) represents a complete loss-of-function, and that a quantitative reduction in DMT1 expression is the cause of the microcytic anemia and iron overload in the patient.
The early onset of iron overload indicates that, as in animal models, DMT1 is dispensable for liver iron uptake, whereas its deficiency in the gut is likely bypassed by the up-regulation of other pathways of iron use.
We investigated whether genetic variability within the DMT1 gene may partly explain the phenotypic variability seen amongst a group of C282Y homozygotes with iron overload.
The importance of DMT1 function at the level of the whole organism and the individual cell and mechanisms of its regulation on a molecular scale are only beginning to be understood; an appreciation of these process will lead to an understanding of the role of iron in various cellular processes and improved treatments for both anemia and iron-overload.
In conclusion, the lack of correlation between DMT1 and Ireg1 protein expression and the liver iron content suggests that elevated duodenal iron transporter expression is not required for high liver iron overload.
The identification of the HFE gene and the apical iron transporter divalent metal transporter-1, DMT-1, provide a direct method to address the mechanisms of iron overload in this disease.
Using quantitative PCR, we measured mRNA expression of divalent cation transporter 1 (DCT1), iron-regulated gene 1 (IREG1), and hephaestin in duodenal biopsy samples of individuals with normal iron levels, iron-deficiency anemia, or iron overload.
The remaining question is whether hemochromatosis probands in our study have iron overload because of environmental factors or due to mutation in gene(s) other than HFE and Nramp2.
Increased NRAMP-2 mRNA expression in duodenal mucosa of patients with hereditary haemochromatosis may promote duodenal iron uptake and lead to iron overload.