title: Exploration of the copper-related compensatory response in the Belgrade rat model of genetic iron deficiency.
abstract: The Menkes copper ATPase (Atp7a) and metallothionein (Mt1a) are induced in the duodenum of iron-deficient rats, and serum and hepatic copper levels increase. Induction of a multi-copper ferroxidase (ceruloplasmin; Cp) has also been documented. These findings hint at an important role for Cu during iron deficiency. The intestinal divalent metal transporter 1 (Dmt1) is also induced during iron deficiency. The hypothesis that Dmt1 is involved in the copper-related compensatory response during iron deficiency was tested, utilizing a mutant Dmt1 rat model, namely the Belgrade (b/b) rat. Data from b/b rats were compared with phenotypically normal, heterozygous +/b rats. Intestinal Atp7a and Dmt1 expression was increased in b/b rats, whereas Mt1a expression was unchanged. Serum and liver copper levels did not increase in the Belgrades nor did Cp protein or activity. The lack of fully functional Dmt1 may thus partially blunt the compensatory response to iron deficiency by 1) decreasing copper levels in enterocytes, as exemplified by a lack of Mt1a induction and a lesser induction of Atp7a, 2) abolishing the frequently described increase in liver and serum copper, and 3) attenuating the documented increase in Cp expression and activity.
authors.affiliation: Food Science & Human Nutrition Department, University of Florida, Gainesville, 32611, USA.
authors.forename: Lingli
authors.initials: L
authors.lastname: Jiang
authors.forename: Perungavur
authors.initials: P
authors.lastname: Ranganathan
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Changae
authors.initials: C
authors.lastname: Kim
authors.forename: James F
authors.initials: JF
authors.lastname: Collins
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D000090463:Iron Deficiencies; D008099:Liver / Q000378:metabolism*; D051381:Rats; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000099236:Solute Carrier Family 11, Member 2