Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kim, B-E; Turski, ML; Nose, Y; Casad, M; Rockman, HA; Thiele, DJ
Published Date
- May 5, 2010
Published In
Volume / Issue
- 11 / 5
Start / End Page
- 353 - 363
PubMed ID
- 20444417
Pubmed Central ID
- PMC2901851
Electronic International Standard Serial Number (EISSN)
- 1932-7420
Digital Object Identifier (DOI)
- 10.1016/j.cmet.2010.04.003
Language
- eng
Conference Location
- United States