Changes of the mRNA expression pattern of Zn transporters: a probable mechanism for cadmium retention and zinc redistribution in the suckling rat tissues

Biol Trace Elem Res. 2015 Jun;165(2):173-82. doi: 10.1007/s12011-015-0255-1. Epub 2015 Feb 5.

Abstract

The present study was conducted to provide potential mechanism that may be responsible for Cd retention and Cd-induced Zn redistribution in tissues of suckling rat. For this purpose, suckling rats from mother receiving either tap water, Cd, or Cd + Zn during lactation period were sacrificed on postnatal day (PND) 14 and PND 21 for performing chemical and molecular analysis. Our results show that Cd exposure, although it does not affect the milk consumption, it clearly alters the lactational transfer, absorption, and distribution of Zn in the suckling rat organism. At the molecular level, Cd caused upregulation of ZIP 3, ZIP 4, and ZIP 8 gene expressions in the mammary gland of mothers rats and in the intestine of their pups but decreased the expression of ZnT 2 and ZnT 4 only in the mammary tissue at PND 14 and PND 21. Zn supply reversed the Cd-induced decrease in the neonatal Zn apparent absorption and restores the gastrointestinal, brain, and plasma levels of this essential element in the suckling rat organism at PND 14 and PND 21. Also, with this treatment, the gene expressions of ZnT 1 in the mammary gland and ZnT 4 in the neonatal intestine were found to be upregulated at PND 21. Furthermore, our results show that Cd or Cd + Zn treatment increase the neonatal hepatic MTs accumulation at PND 14 only. These results imply that the downregulation of ZnT as well as the overexpression of ZIP transporters, in responses to the Zn depletion induced by Cd in the tissues of lactating rat and their offspring, play a major role in Cd accumulation and Zn redistribution in tissues of suckling rat.

MeSH terms

  • Animals
  • Animals, Suckling
  • Cadmium / chemistry*
  • Carrier Proteins / metabolism
  • Cation Transport Proteins / metabolism*
  • Female
  • Gene Expression Regulation*
  • Heat-Shock Proteins / metabolism
  • Lactation
  • Male
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / metabolism
  • Membrane Transport Proteins
  • Metallothionein / metabolism
  • Milk / chemistry
  • Rats
  • Rats, Wistar
  • Sequestosome-1 Protein
  • Zinc / chemistry*

Substances

  • Carrier Proteins
  • Cation Transport Proteins
  • Heat-Shock Proteins
  • Membrane Transport Proteins
  • Sequestosome-1 Protein
  • Slc30a2 protein, rat
  • Slc30a4 protein, rat
  • Slc39a4 protein, rat
  • Slc39a8 protein, rat
  • Sqstm1 protein, rat
  • Cadmium
  • Metallothionein
  • Zinc