American Journal of Clinical Nutrition, Vol 67, 988S-995S, Copyright © 1998 by The American Society for Clinical Nutrition, Inc

REVIEW ARTICLES

Functional analysis of copper homeostasis in cell culture models: a new perspective on internal copper transport

ED Harris, Y Qian, E Tiffany-Castiglioni, AR Lacy and MC Reddy
Department of Biochemistry and Biophysics and the Faculty of Nutrition, Texas A&M University, College Station 77843-2128, USA. eharris@bioch.tamu.edu

The movement of copper ions across membrane barriers of vital organs and tissues is a priority topic in nutrition and one for which there continues to be little understanding of the mechanism. Reports of membrane-bound, copper-transporting adenosine triphosphatases (Cu- ATPases) selective for copper ions have brought new focus to the problem and prompted fresh ideas. Using a cell culture model approach, we attempted to learn whether transport into and out of cells depends on a Cu-ATPase. Measurement of transport kinetics in fibroblasts, brain glial cells, neuroblastoma cells, and placental cells showed differences in the rates of copper uptake and response to sulfhydryl reagents. BeWo cells, a human choriocarcinoma placental cell line, behaved as did Menkes fibroblasts by avidly absorbing copper but not releasing copper to the immediate environment. Further tests showed that BeWo cells did not express the transcript for the membrane-bound Cu-ATPase that has been identified with Menkes syndrome. Transcript induction, however, was achieved by growing BeWo cells on porous filters that allowed apical and basolateral surfaces to form. With transcript expression, the cells showed a capacity to release copper into the medium. BeWo cells also synthesized a form of ceruloplasmin whose structure differed from that of the plasma protein and hence may be a product of a different gene. BeWo cells may also express the gene for Wilson disease, thus linking Menkes and Wilson proteins to maternal delivery of copper. We constructed a model in which both ATPases work in concert in a vesicle-based transport mechanism. The vesicle model may help us understand the transport of copper across the placenta and all cells in general.

This article has been cited by other articles:

				G. Samimi, K. Katano, A. K. Holzer, R. Safaei, and S. B. Howell Modulation of the Cellular Pharmacology of Cisplatin and Its Analogs by the Copper Exporters ATP7A and ATP7B Mol. Pharmacol., July 1, 2004; 66(1): 25 - 32. [Abstract] [Full Text] [PDF]

				M. Komatsu, T. Sumizawa, M. Mutoh, Z.-S. Chen, K. Terada, T. Furukawa, X.-L. Yang, H. Gao, N. Miura, T. Sugiyama, et al. Copper-transporting P-Type Adenosine Triphosphatase (ATP7B) Is Associated with Cisplatin Resistance Cancer Res., March 1, 2000; 60(5): 1312 - 1316. [Abstract] [Full Text]

				A. R. White, G. Multhaup, F. Maher, S. Bellingham, J. Camakaris, H. Zheng, A. I. Bush, K. Beyreuther, C. L. Masters, and R. Cappai The Alzheimer's Disease Amyloid Precursor Protein Modulates Copper-Induced Toxicity and Oxidative Stress in Primary Neuronal Cultures J. Neurosci., November 1, 1999; 19(21): 9170 - 9179. [Abstract] [Full Text] [PDF]

				A. Bianchini, G. Musci, and L. Calabrese Inhibition of Endothelial Nitric-oxide Synthase by Ceruloplasmin J. Biol. Chem., July 16, 1999; 274(29): 20265 - 20270. [Abstract] [Full Text] [PDF]