Your browser doesn't support javascript.
loading
Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade (b) rat.
Ferguson, Carole J; Wareing, Mark; Delannoy, Mathieu; Fenton, Robert; McLarnon, Stuart J; Ashton, Nicholas; Cox, Alan G; McMahon, Raymond F T; Garrick, Laura M; Green, Roger; Smith, Craig P; Riccardi, Daniela.
Afiliação
  • Ferguson CJ; School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Kidney Int ; 64(5): 1755-64, 2003 Nov.
Article em En | MEDLINE | ID: mdl-14531808
BACKGROUND: We have previously shown that the rat kidney reabsorbs metabolically significant amounts of iron and that it expresses the divalent metal transporter 1, DMT1. The Belgrade (b) rat carries a mutation in DMT1 gene, which causes hypochromic, microcytic anemia due to impaired intestinal iron absorption and transport of iron out of the transferrin cycle endosome. In the duodenum of b/b rats, expression of DMT1 mRNA and protein is increased, suggesting a feedback regulation by iron stores. The aim of this study was to investigate iron handling and DMT1 expression in the kidneys of Belgrade rats. METHODS: Animals were maintained for 3 weeks on a synthetic diet containing 185 mg/kg iron (FeSO4), after which functional and molecular parameters were analyzed in male heterozygous (+/b) and homozygous (b/b) rats (N = 4 to 6 for each group). RESULTS: Serum iron concentration was significantly higher in b/b compared to +/b rats while urinary iron excretion rates were unchanged in b/b compared to +/b rats. Northern analysis using a rat DMT1 probe showed comparable mRNA levels between +/b and b/b animals. Western analysis and immunofluorescence microscopy performed using a polyclonal antibody against rat DMT1 showed that DMT1-specific immunoreactivity was almost absent in the kidneys of b/b rats compared to that seen in +/b animals. CONCLUSION: Our results indicate that the G185R mutation of DMT1 causes protein instability in the kidneys of b/b rats. Given that +/b and b/b rats excrete comparable amounts of iron, the lack of DMT1 protein is compensated by an alternative, yet to be identified, mechanism.
Assuntos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Proteínas de Transporte de Cátions / Proteínas de Ligação ao Ferro / Anemia / Ferro / Rim Limite: Animals Idioma: En Ano de publicação: 2003 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Proteínas de Transporte de Cátions / Proteínas de Ligação ao Ferro / Anemia / Ferro / Rim Limite: Animals Idioma: En Ano de publicação: 2003 Tipo de documento: Article