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Title: REDUCTION OF THE RELATIVE AMOUNT OF ARP7A MRNA IN THE INTESTINAL MUCOSA CELLS OF RATS MADE COPPER DEFICIENT BY FEEDING THEM A HIGH-ZINC DIET

Author
item Reeves, Phillip

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 8/18/2001
Publication Date: 8/18/2001
Citation: Reeves, P.G. 2001. Reduction of the relative amount of ARP7A MRNA in the intestinal musoca cells of rats made copper deficient by feeding them a high-zinc diet [abstract]. Presented at Federation of American Societies for Experimental Biology Conference, Saxton River, VT, August 18-23, 2001.

Interpretive Summary:

Technical Abstract: Feeding high-Zn diets to animals or humans induces the signs of copper deficiency. Although it was once thought that high concentrations of Zn- induced metallothionein (MT) in the intestinal mucosa bound Cu and prevented its transport into the circulation, we showed that MT-null mice also develop signs of Cu deficiency when fed high-Zn diets. Thus, it seems that a simple competition between Zn and Cu for transport sites is not the answer. We designed the following experiment to determine if the mechanism might involve a Zn effect on the function of the Cu transport protein ATP7a. Does feeding excess dietary Zn to rats reduce the relative concentrations of ATP7a mRNA and protein in the intestinal mucosa? Weanling male rats were fed diets with either 30 or 450 mg Zn/kg for 5 weeks. At that time the rats were killed and the Cu status assessed by measuring the activity of the Cu containing plasma protein, ceruloplasmin. The effects on relative amounts of ATP7a mRNA were assessed by scraping th mucosal cells, isolating RNA, and performing a relative quantitative RT-PCR assay by using 18S rRNA as the internal standards. Results showed that rats consuming the high-Zn diet for 5 weeks had plasma ceruloplasmin activities about 60% of those in rats consuming the normal Zn diet. This indicates that the absorption of Cu was indeed reduced in the high-Zn fed rats. In addition, the RT-PCR assays showed that the relative abundance of ATP7a mRNA in the mucosal cells of the high-Zn fed rats was only 40% of that in rats fed normal-Zn diets. This indicates that the high-Zn treatment down- regulated the expression of the message for the copper transporter. Whether this would translate into a reduction in the amount of transporter protein is still to be determined.