Cardiac Copper Deficiency Activates a Systemic Signaling Mechanism That Communicates with the Copper Acquisition and Storage Organs

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2010 May 7

PMID 20444417

Citations 85

Authors

Byung-Eun Kim

Michelle L Turski

Yasuhiro Nose

Michelle Casad

Howard A Rockman

Dennis J Thiele

Affiliations

Soon will be listed here.

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.

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