title: Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs.
abstract: Copper (Cu) is an essential cofactor for a variety of metabolic functions, and the regulation of systemic Cu metabolism is critical to human health. Dietary Cu is absorbed through the intestine, stored in the liver, and mobilized into the circulation; however, systemic Cu homeostasis is poorly understood. We generated mice with a cardiac-specific knockout of the Ctr1 Cu transporter (Ctr1(hrt/hrt)), resulting in cardiac Cu deficiency and severe cardiomyopathy. Unexpectedly, Ctr1(hrt/hrt) mice exhibited increased serum Cu levels and a concomitant decrease in hepatic Cu stores. Expression of the ATP7A Cu exporter, thought to function predominantly in intestinal Cu acquisition, was strongly increased in liver and intestine of Ctr1(hrt/hrt) mice. These studies identify ATP7A as a candidate for hepatic Cu mobilization in response to peripheral tissue demand, and illuminate a systemic regulation in which the Cu status of the heart is signaled to organs that take up and store Cu.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Byung-Eun
authors.initials: BE
authors.lastname: Kim
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Turski
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nose
authors.forename: Michelle
authors.initials: M
authors.lastname: Casad
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rockman
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D004330:Drosophila / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C490077:Slc31a1 protein, mouse; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases
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