Copper treatment alters the barrier functions of human intestinal Caco-2 cells.
- Author:
Zhi-wei LIU
1
;
Jia-lin CHEN
;
Bing-heng CHEN
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Biological Transport; Caco-2 Cells; Cell Membrane Permeability; drug effects; Copper; toxicity; Humans
- From: Chinese Journal of Preventive Medicine 2004;38(6):406-410
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of copper on permeability and P-glycoprotein (P-gp) of Caco-2 cell monolayers.
METHODSThe differentiated Caco-2 cell model was used in this study. Permeability of cell monolayers was reflected by monitoring transepithelial electrical resistance (TEER); distribution of tight junctional protein ZO-1 was measured by immunofluorescent staining; F actin was measured by fluorescence staining; and Activity of P-gp was reflected by changes of transcellular transport and accumulation of Rho-123 in Caco-2 cells.
RESULTSApical treatment with copper (30 - 100 micromol/L, Hanks' buffered salt solution, up to 3 hours) induced a time- and concentration-dependent increase in permeability reflected by progressive decrease of TEER of Caco-2 cell monolayers, accompanied by deorganization of F actin, but without significant effects on tight junctional protein ZO-1; at a dose without any adverse effects on viability and permeability of Caco-2 monolayers, copper treatment (300 micromol/L, complete medium, 24 hours) decreased Papp(BL-->AP) from 7.37 +/- 0.20 x 10(-6) cm/s (controls) to (6.43 +/- 0.27) x 10(-6) cm/s, the increased Papp(AP-->BL) from (1.23 +/- 0.05) x 10(-7) cm/s (controls) to (3.41 +/- 0.08) x 10(-7) cm/s, and enhanced the intracellular Rho-123 from (0.31 +/- 0.01) nmol/filter (controls) to (0.50 +/- 0.03) nmol/filter.
CONCLUSIONCopper might alter the barrier functions of Caco-2 cells through increasing the permeability and inhibiting P-gp of Caco-2 cells.
