Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells

Biochem Pharmacol. 2000 Mar 1;59(5):467-70. doi: 10.1016/s0006-2952(99)00366-4.

Abstract

Treatment of Caco-2 cells with the antioxidants quercetin or t-butylhydroquinone led to induced protein levels of UDP-glucuronosyltransferase UGT1A6 (ca. 3-fold over controls) and of the apical conjugate export pump multidrug resistance protein 2 (MRP2; 1.9-fold over controls). In contrast to UGT1A6, MRP2 (symbol ABCC2) was not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Immunocytochemistry demonstrated that MRP2 was only expressed at the brush border domain of Caco-2 cell monolayers. The results indicate that UGT1A6 and MRP2 are coordinately induced by antioxidants, facilitating chemoprotection against phenolic toxins and excretion of conjugates into the intestinal lumen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / biosynthesis*
  • ATP-Binding Cassette Transporters / biosynthesis*
  • Antioxidants / pharmacology
  • Caco-2 Cells
  • Glucuronosyltransferase / biosynthesis*
  • Humans
  • Immunoblotting
  • Membrane Transport Proteins*
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Polychlorinated Dibenzodioxins / pharmacology
  • Quercetin / pharmacology
  • Receptors, Aryl Hydrocarbon / agonists
  • Teratogens / pharmacology

Substances

  • ABCC2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Antioxidants
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Teratogens
  • Quercetin
  • UDP-glucuronosyltransferase, UGT1A6
  • Glucuronosyltransferase
  • multidrug resistance-associated protein 1