Copper storage diseases: Menkes, Wilsons, and cancer.

Abstract

The trace element copper is vital to the healthy functioning of organisms. Copper is used in a multitude of cellular activities including respiration, angiogenesis, and immune responses. Like other metals, copper homeostasis is a tightly regulated process. Copper is transported from dietary intake through the serum and into cells via a variety of transporters. There are a variety of copper chaperones designed to insure that copper is sequestered from interaction with cellular membranes, proteins, or DNA where its properties can result in oxidative damage. However, there are disease states in which copper transporters crucial to homeostasis are impaired resulting in potentially toxic copper accumulation. Wilsons and Menkes diseases are two such cases. Wilsons disease (hepatolenticular degeneration) is an autosomal recessive disorder resulting in extreme accumulation of copper in the liver with deposits elsewhere in the body. Menkes is characterized by a systemic copper deficiency (different from the liver specificity of Wilsons disease) and is the result of an X-linked recessive mutation in a copper transporter. Uptake of copper is impaired due to inability to remove existing copper from cells primarily in the small intestine. Though the causes are dramatically different, cancer also shares a similar diagnostic in the accumulation of copper in effected tissues. Studies have shown greatly elevated levels of copper in cancer tissues, and some diagnostics and treatments from Wilsons and Menkes diseases, such as copper chelation therapy, have been used in the treatment of cancer. Given the commonality of copper accumulation in these diseases and that common therapies exist between them, it may prove beneficial to study all three diseases in light of copper homeostasis. This review will examine the chemical nature and biological roles of copper, Wilsons and Menkes disease and their therapies, and the use of copper related therapies in cancer.

• Authors: Kenyon G Daniel, R Hope Harbach, Wayne C Guida, Q Ping Dou
• Journal: Frontiers in bioscience : a journal and virtual library (Front Biosci) Vol. 9 Pg. 2652-62 (Sep 01 2004) ISSN: 1093-9946 [Print] United States
• PMID: 15358588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Chelating Agents
• Ligands
• Copper
• Proteasome Endopeptidase Complex
• Oxygen

Topics

• Animals
• Chelating Agents (pharmacology)
• Copper (metabolism)
• Drug Design
• Hepatolenticular Degeneration (diagnosis, pathology)
• Humans
• Ligands
• Menkes Kinky Hair Syndrome (diagnosis, pathology)
• Mutation
• Neoplasms (diagnosis, pathology)
• Oxidative Stress
• Oxygen (metabolism)
• Proteasome Endopeptidase Complex (metabolism)