Basal expression of copper transporter 1 in intestinal epithelial cells is regulated by hypoxia-inducible factor 2α

FEBS Lett. 2012 Jul 30;586(16):2423-7. doi: 10.1016/j.febslet.2012.05.058. Epub 2012 Jun 7.

Abstract

Hypoxia, via stabilization of HIF2α, regulates the expression of the intestinal iron transporters DMT1 and ferroportin. Here we investigated whether the intestinal copper importer Ctr1 was also regulated by hypoxia. Copper uptake and Ctr1 mRNA expression were significantly increased in Caco-2 cells exposed to hypoxia. To determine whether HIF2α was involved in regulation of Ctr1 expression, we employed three models of HIF2α knockdown (chemical suppression of HIF2α translation in Caco-2 cells; HIF2α-siRNA-treated HuTu80 cells; HIF2α-intestinal knockout mice); Ctr1 mRNA expression was decreased in all three models under normoxic conditions. HIF2α translational inhibitor did not alter Ctr1 expression under hypoxic conditions. We conclude that basal expression of Ctr1 is regulated by HIF2α; however, the induction by hypoxia is a HIF2α-independent event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Caco-2 Cells
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Copper / pharmacology
  • Copper Transporter 1
  • Duodenum / metabolism
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation*
  • Homeostasis
  • Humans
  • Hypoxia
  • Intestinal Mucosa / metabolism*
  • Iron / pharmacology
  • Mice
  • Mice, Knockout

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cation Transport Proteins
  • Copper Transporter 1
  • SLC31A1 protein, human
  • Slc31a1 protein, mouse
  • endothelial PAS domain-containing protein 1
  • Copper
  • Iron