|Briske Anderson, Mary|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/1998
Publication Date: N/A
Citation: Interpretive Summary: Metallothionein (MT) is a relatively small molecule that binds heavy metals including silver, cadmium, copper and zinc, and is made by most cells in our body. Its production can be induced in the intestinal cells where it is thought to help keep us from absorbing a lot of toxic heavy metals such as cadmium. MT is also thought to be involved in the regulation of the cellular concentration of the essential minerals copper and zinc. The lining of our blood vessels is made up of a specific cell type called endothelial cells. Whereas the intestinal cell is the first barrier to the absorption of minerals, the endothelial cells are the secondary barrier to getting minerals into our tissues and organs. The question we asked, does MT help to regulate the movement of zinc from the blood to the tissues, and does it contribute to the regulation of zinc in these cells? Studies with endothelial cells are relatively easy to perform because this type of cell can be readily grown in culture conditions in a test tube outside the body. When the cells were grown in culture media (fluid plus nutrients) with higher than normal amounts of zinc (10 times the amount found in blood), they made large amounts of MT. However in moderate concentrations of zinc (2 to 5 times normal), MT was not increased. The concentration of zinc in the cell itself was clearly associated with the amount of MT at the higher concentrations of zinc in the fluid bathing the cells, but it was not associated with MT at the lower concentrations of media zinc. The data suggest that the amount of MT in the endothelial cell is not promoted by zinc concentrations (in the normal physiological range) outside the cell, and that the amount of zinc in the cell is not regulated by changing the MT concentrations.
Technical Abstract: Endothelial cells were grown in vitro under a variety of conditions to examine possible scenarios of metallothionein (MT) participation in zinc homeostasis. Cell culture models included serum to approximate the physiological milieu that exists in vivo. MT was increased by 200 uM zinc in the extracellular environment. MT was relatively insensitive to 50 to 100 uM zinc, even after 24 h of exposure. Endothelial cells had reduced MT content when grown in medium comprised of serum that had been dialyzed to remove components with molecular mass of less than 1000, including zinc and other minerals. Major minerals were restored and their concentrations in the final medium were not significantly different from those in the original medium. Restoring the zinc concentration in the medium with dialyzed serum did not restore MT content in the cells. In longitudinal studies, the MT concentration was highest soon after the culture was initiated, i.e., when the cells were rapidly dividing. Forty-eight hr incubations of cells with IL-6 and dexamethasone increased cellular MT; however, 17 beta-estradiol decreased MT, and IL-1 and cAMP had no discernible effect. We conclude that MT is constitutively expressed in endothelial cells, but extracellular zinc concentration is not the predominant promoter of MT concentration in these cells under typical physiological conditions. Zinc homeostasis by endothelial cells is not maintained by changing the MT concentration in response to changes in the extracellular zinc environment.