Expression of MRP1 and related transporters in human lung cells in culture.

Abstract:

:Multidrug resistance type 1 P-glycoproteins (P-gp) and multidrug resistance associated proteins (MRP) were studied in differentiated primary human lung cells in culture, in comparison with permanent human lung cell lines and primary alveolar type II cells from rat lung. AII cells exhibited low basal levels of mdr1b mRNA, that increased over time and after oxygen radical production induced by paraquat. mRNAs coding for antioxidative enzymes catalase (CAT), maganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) were not changed. H358, A549, H322 cells expressed low levels of MDR1 mRNA, but the mdr1 substrate rhodamine 123 (Rh 123) was transported out of H358 and H322 cells in a non-invasive, single cell fluorescence assay. The dye efflux could be inhibited by the chemosensitizer, verapamil. Normal human bronchial epithelial cells (NHBEC) expressed immuno-reactive MDR1 P-gp and the MPR protein that was active in the fluorescence assay using the MRP substrate carboxy-dichlorofluorescein (CDF) and MK-571 as an inhibitor. We did observe inter-individual variation of MRP in both the mRNA and the immunoreactive protein in NHBEC culture. Over time (12 weeks) the protein was relatively stable in NHBEC and epithelial cells from peripheral lung (PLC), but the mRNA level was drastically increased when explant cultures were continued (18 weeks).

journal_name

Toxicology

journal_title

Toxicology

authors

Lehmann T,Köhler C,Weidauer E,Taege C,Foth H

doi

10.1016/s0300-483x(01)00458-9

keywords:

subject

Has Abstract

pub_date

2001-10-05 00:00:00

pages

59-72

issue

1

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(01)00458-9

journal_volume

167

pub_type

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