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Copper treatment alters the barrier functions of human intestinal Caco-2 cells: involving tight junctions and P-glycoprotein

Department of Environmental Health, School of Public Health, Fudan University, Box 249, 138 Yixueyuan Road, Shanghai 200032, P.R. China Lzw7675{at}yahoo.com.cn

Bingheng Chen

Department of Environmental Health, School of Public Health, Fudan University, 200032 Shanghai P.R. China

This study investigated the effects of copper on paracellular permeability and P-glycoprotein (P-gp) in Caco-2 cells. Apical treatment with 100–300,µM CuS0₄ in Hanks' balanced salt solution (HBSS, up to 3 hours) induced a time-and concentration-dependent increase in permeability of Caco-2 cell monolayers monitored by transepithelial electrical resistance (TEER). Copper treatment also induced a concentration-dependent reduction of F-actin stain, but not of tight junctional protein ZO-1. In addition, without any adverse effects on TEER, apical treatment with 300 µM CuS0₄ in complete medium (for 24 hours) could reduce basolateral-to-apical transport, and increase apical-to-basolateral transport of rhodamine-123 (Rho-123) and accumulation of Rho-123 in Caco-2 cells. Treatment with 10-100 µM CuS0₄ in HBSS (up to 3 hours) also induced a time-and concentration-dependent increase in accumulation of Rho-123 in Caco-2 cells. The results indicated that copper treatment increased the paracellular perme-ability probably by perturbing F-actin skeleton, and inhibited P-gp, thus altering the barrier functions of Caco-2 cells.

Key Words: Caco-2 cells • copper • P-glycoprotein • tight junction

Human & Experimental Toxicology, Vol. 23, No. 8, 369-377 (2004)
DOI: 10.1191/0960327104ht464oa


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