Basal expression of copper transporter 1 in intestinal epithelial cells is regulated by hypoxia-inducible factor 2α.
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.
Diabetes & Nutritional Sciences Division, King's College London, London, UK.
Katayoun
K
Pourvali
Pavle
P
Matak
Gladys O
GO
Latunde-Dada
Solomis
S
Solomou
Maria
M
Mastrogiannaki
Carole
C
Peyssonnaux
Paul A
PA
Sharp
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003300:Copper / Q000494:pharmacology; D000079923:Copper Transporter 1; D004386:Duodenum / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia; D007413:Intestinal Mucosa / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins; D003300:Copper; D000079923:Copper Transporter 1; D007501:Iron; D000099162:Endothelial PAS Domain-Containing Protein 1; C490079:SLC31A1 protein, human; C490077:Slc31a1 protein, mouse