Rat Slc11a2 (Natural resistance-associated macrophage protein 2) ELISA Kit

Divalent cations are strongly implicated in Alzheimer's disease (AD) pathogenesis, and can regulate amyloid beta-peptide aggregation. The proton-divalent cation transporters encoded by SLC11A1 (formerly NRAMP1) on chromosome 2q35, and SLC11A2 (also known as DCT1 and DMT1) on chromosome 12q13, are expressed in the brain and regulate ion homeostasis from endosomal compartments. SLC11A1 also has pleiotropic effects on pro-inflammatory responses that may be important in AD. We analyzed seven informative polymorphisms in the SLC11A1 and SLC11A2 genes encoding these divalent cation transporters in a sample of 216 late-onset AD cases and 323 age-matched controls. We found only borderline evidence (p = 0.08) for an allelic association between SNP rs407135 at SLC11A2 and AD, in which the variant allele was protective (odd ratio (OR) 0.77; 95% CI 0.56-1.04) relative to the more common allele. There was no interaction with apolipoprotein E (APOE) epsilon 4 but stratification by gender showed that all of the effect of SLC11A2 was in the male patient group. No other associations with AD were observed at SLC11A1 or SLC11A2, indicating no major effect of either gene for the occurrence of AD. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Background: Divalent metal-ion transporter 1 (DMT1) may transport copper, but studies to date on this topic have been equivocal. Previously, an ex vivo experiment showed that intestinal copper transport was impaired in Dmt1-mutant Belgrade rats. Objective: In this study, we tested the hypothesis that intestinal DMT1 transports copper in vivo. Methods: Intestine-specific Dmt1 knockout (Dmt1(int/int)) mice and normal (control) littermates (Dmt1(fl/fl)) were used. In study 1, intestinal copper absorption was assessed in 7-wk-old mice of both sexes and genotypes by oral-intragastric gavage of Cu-64 under normal and iron-deficiency anemia (IDA) conditions. In study 2, both sexes and genotypes of 8-wk-old mice were fed diets with adequate iron concentrations [72 parts per million (ppm)] plus adequate (9 ppm) or excessive (183 ppm) copper concentrations for 4 wk. Iron-and copper-related physiologic variables were subsequently assessed. Results: Study 1 showed that intestinal copper transport was enhanced in normal (similar to 11% increase in males, 35% in females) and anemic (similar to 42% increase in males, 35% in females) Dmt1(int/int) mice. Study 2 showed that, with adequate copper intakes, serum ceruloplasmin (Cp) activity was decreased (by similar to 29% in males and 20% in females) and spleens were enlarged (by 3-fold in both sexes) in Dmt1(int/int) mice. Higher dietary copper increased hepatic copper concentrations (by similar to 3.3-fold in males and 1.5-fold in females), restored serum Cp activity, and mitigated the noted splenomegaly in Dmt1(int/int) mice. Conclusions: Copper homeostasis was disrupted in Dmt1(int/int) mice, particularly during IDA, despite the noted increases in intestinal copper transport. This was exemplified by the fact that extra dietary copper was required to restore serum Cp activity (a biomarker of copper status) and reduce the severity of the noted splenomegaly (which could reflect changes in erythropoietic demand) in Dmt1(int/int) mice. Collectively, these observations show that intestinal DMT1 is essential for the assimilation of sufficient quantities of dietary copper to maintain systemic copper homeostasis during IDA.