UF Researchers Identify Zinc Transport Proteins

By:
Tom Nordlie (352) 392-1773 x 278

Source(s):
Bob Cousins cousins@ufl.edu, (352) 392-1991 ext. 222

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GAINESVILLE, Fla.—When infections strike people and other mammals, zinc circulating in their blood is diverted into liver cells, a response both familiar and puzzling to scientists, who have long debated its purpose.

University of Florida researchers studying mice have, for the first time, identified proteins that transport zinc during the process, said Robert Cousins, an eminent scholar of nutritional biochemistry with UF’s Institute of Food and Agricultural Sciences. The researchers also identified the chemical that initiates production of the most active protein in the group.

The findings, published in a recent issue of the journal “Proceedings of the National Academy of Sciences,” may eventually help scientists determine whether the zinc is mobilized as a survival strategy, he said.

“The current thinking is there’s some benefit to redistributing the zinc,” said Cousins, a member of the National Academy of Sciences and an internationally recognized expert on dietary zinc. “It may be liver cells need extra zinc to carry out their functions, or perhaps reducing zinc levels in the blood discourages the growth of infectious organisms.”

Though it may take years to fully understand why the body sends zinc to the liver, the UF study shows how advances in genetics research might enable scientists to solve the riddle faster, he said.

“We screened all the genes that had been identified as possibly controlling cellular zinc transport, and identified the important ones by process of elimination,” Cousins said. “This same approach could help narrow down the list of theories about why it happens.”

Important to immune responses, wound healing and reproduction, zinc is the second most abundant trace mineral in the human body, after iron, he said. In most adults, a total of 1.5 to 2.5 grams of zinc is found in muscles, blood, bone and some organs.

The human body contains more than 20 proteins that transport zinc, each produced at the direction of a different gene, Cousins said. Researchers are uncertain why people make so many of the proteins, or whether they all have unique functions.

“It’s odd, because in iron metabolism, for example, there are only two transport proteins — one to take iron into cells and one to bring it out,” he said. “With zinc, the theory is that this nutrient does so many things that some of the transporters may be used only for specific processes inside cells. For example, zinc is needed by the pancreas to process and secrete insulin to prevent diabetes.”

With funding from a long-term National Institutes of Health grant, Cousins has set out to learn the secrets of every gene associated with zinc transport, as well as the physiological events that influence the genes’ activity.

“The zinc redistribution process that occurs during infection is well-known, so it was a good place for us to start,” said Cousins, who is based in UF’s Department of Food Science and Human Nutrition.

In the current study, Cousins, along with department colleagues Juan Liuzzi, a post-doctoral associate, and Mitchell Knutson, an assistant professor of nutritional biochemistry, worked with collaborators at the University of California, Los Angeles. The research team determined that three proteins, known as ZnT5, Zip6 and Zip14, transported zinc in response to both infection and inflammation, which also causes zinc to accumulate in liver cells.

To make the discovery, the researchers screened 14 zinc transport genes using two groups of mice, inducing infection in one group and causing inflammation in the other. Later, genetic analysis of liver cells from the mice showed the genes that control production of ZnT5, Zip6 and Zip14 became significantly more active in both groups. The researchers then focused on the Zip14 gene, which had the strongest response.

Previous studies had suggested this redistribution of body zinc to the liver is initiated by the protein interleukin 6, which directs many of the body’s defenses to acute illness. To explore this possibility, the researchers conducted an experiment in mice lacking the gene that controls production of interleukin 6. These so-called knockout mice showed little zinc transfer to liver cells when exposed to infection or inflammation, suggesting that without interleukin 6 the Zip14 gene remains inactive.

In the future, these UF researchers plan to explore whether the known minor variations in the Zip14 gene might cause differences in the way people process and respond to zinc, Cousins said. Physicians might one day be better able to treat patients suffering infections, if it were possible to gauge how much zinc each person required for an optimum infection-fighting response.

“We’re at the beginning of this work, but it’s exciting because many of these genes have been identified only in the past few years, and using new digital imaging methods in microscopy we’re able to see things no one else has ever seen,” he said.

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Posted: July 6, 2005


Category: UF/IFAS



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