Copper treatment alters the barrier functions of human intestinal Caco-2 cells: involving tight junctions and P-glycoprotein.
This study investigated the effects of copper on paracellular permeability and P-glycoprotein (P-gp) in Caco-2 cells. Apical treatment with 100-300 microM CuSO4 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 microM CuSO4 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 microM CuSO4 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 permeability probably by perturbing F-actin skeleton, and inhibited P-gp, thus altering the barrier functions of Caco-2 cells.
Liu
Zhiwei
Z
Department of Environmental Health, School of Public Health, Fudan University, 200032 Shanghai, PR China. Lzw7675@yahoo.com.cn
Chen
Bingheng
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D018938:Caco-2 Cells; D003300:Copper / Q000633:toxicity*; D003599:Cytoskeleton / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D010539:Permeability; D019108:Tight Junctions / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000199:Actins; D003300:Copper