Rabbit Anti-Human SLC11A2 (internal) Polyclonal antibody

Natural resistance associated macrophage protein 2 plays an important role in adsorption of a broad range of divalent metal ions, including iron, cobalt, zinc, copper, nickel, manganese, cadmium and lead. The protein contains 12 putative transmembrane domains, two highly conserved and mutation sensitive histidines were found in the predicted transmembrane domain 6, mutation of two histidines at either or both sites causing deficiency of function. In this paper, the structure of the peptide from transmembrane 6 of natural resistance associated macrophage protein 2 was investigated in 60% hexafluoroisopropanol aqueous solution by circular dichroism and nuclear magnetic resonance spectroscopy. Our study demonstrated the peptide forms a discontinuous alpha helix structure with two helices spanning over Ala256-Ile259 and Asn268-Ser278.

Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD) but the neurodegenerative mechanisms have not been completely elucidated. Iron accumulation in dopaminergic neurons and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation and neuronal death. However, the mechanisms involved in iron accumulation remain unclear. In previous studies we excluded a role of transferrin and its receptor in iron accumulation while we showed that lactoferrin receptors were overexpressed in blood vessels and dopaminergic neurons in Parkinson's disease. We recently also described an increase in the expression of the divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) in the SN of PD patients. Using the PD animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice, we showed that DMT1 expression increased in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress and dopaminergic cell loss. A mutation in DMT1 that impairs iron transport protected rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine (6-OHDA). This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD. (C) 2009 Elsevier Ltd. All rights reserved.