UB Scientist Discovers Novel Iron-Copper Alliance

BUFFALO, N.Y. -- Iron is the workhorse of trace minerals. An essential component of red blood cells, disruption of iron levels in the body will result in a myriad of serious conditions, and life cannot be sustained without it.

In novel research, investigators at the University at Buffalo's School of Public Health and Health Professions, have learned that iron is only one half of an all-important duo of trace minerals -- the other being copper -- that work in tandem to maintain proper iron balance, or homeostasis.

It appears the workhorse has a helper.

James F. Collins, Ph.D., UB assistant professor of exercise and nutrition sciences and biochemistry, discovered that when iron-absorption by cells lining the small intestine decreases during iron-deficient states, copper absorption increases.

Collins now is exploring the relationship between these two trace minerals through a $1.38 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The work will be carried out using established models of intestinal iron absorption in humans, including iron and iron/copper-deficient rodents and cultured intestinal epithelial cells.

"This project is intended to test the overall hypothesis that increased copper transport during iron-deficiency is critical to enhance certain aspects of intestinal iron absorption," said Collins.

"Iron or copper deficiency causes anemia, and abnormal intestinal iron transport is associated with several common human pathologies, including anemia of chronic disease (ACD) and hereditary hemochromatosis (HH), different forms of which result from several common genetic defects."

HH is an inherited metabolic disorder characterized by abnormally high absorption of dietary iron, which is deposited in body tissues and organs, where it may become toxic. ACD is a blood disorder caused by low body iron levels resulting from any medical condition that affects the production and lifespan of red blood cells, such as chronic infection, chronic immune activation resulting in inflammation, or malignancy.

"In collaboration with Dr. Zihua Hu, Ph.D., a computational scientist at UB's New York State Center of Excellence in Bioinformatics and Life Sciences, we determined that several genes related to iron and copper homeostasis were strongly induced by iron deprivation across different developmental stages in the rat small intestine," said Collins. "We will concentrate on understanding the role of two key proteins encoded by these genes: an intestinal iron transporter called divalent metal transporter 1 (Dmt1) and an intestinal copper transporter, the Menkes copper ATPase (Atp7a)."

The overall goal of the project is to answer three specific questions regarding the role of copper in intestinal iron transport, Collins noted: 1) Are Atp7a and Dmt1 solely responsible for enhancing dietary copper absorption during iron-deficiency? 2) What are the molecular mechanisms leading to induction of the Atp7a and Dmt1 genes? and 3) Which physiological processes related to intestinal iron ion homeostasis are enhanced by increased copper levels in enterocytes (cells of the superficial layer of the intestines) and in the liver?

"We also expect to learn more about the mechanisms of dietary copper absorption, which currently are not well defined," Collins said. "Furthermore, studies addressing the impact of increased enterocyte and liver copper levels during iron-deficiency have not been reported in the scientific literature to date, so this investigation is novel. "

Key collaborators at UB are Hu, Michael D. Garrick, Ph.D., professor of biochemistry, and Laura M. Garrick, Ph.D., research associate professor of biochemistry.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities. The School of Public Health and Health Professions is one of five schools that constitute UB's Academic Health Center.