Lower electrical membrane potential and altered pHi homeostasis in multidrug-resistant (MDR) cells: Further characterization of a series of MDR cell lines expressing different levels of P-glycoprotein

Biochemistry ◽  
1993 ◽  
Vol 32 (41) ◽  
pp. 11042-11056 ◽  
Author(s):  
Paul D. Roepe ◽  
Li Yong Wei ◽  
Jonathon Cruz ◽  
Dianne Carlson
1991 ◽  
Vol 11 (8) ◽  
pp. 3940-3948
Author(s):  
C T Wu ◽  
M Budding ◽  
M S Griffin ◽  
J M Croop

Mammalian multidrug-resistant cell lines, selected for resistance to a single cytotoxic agent, display cross-resistance to a broad spectrum of structurally and functionally unrelated compounds. These cell lines overproduce a membrane protein, the P-glycoprotein, which is encoded by a member(s) of a multigene family, termed mdr or pgp. The amino acid sequence of the P-glycoprotein predicts an energy-dependent transport protein with homology to a large superfamily of proteins which transport a wide variety of substances. This report describes the isolation and characterization of two Drosophila homologs of the mammalian mdr gene. These homologs, located in chromosomal sections 49EF and 65A, encode proteins that share over 40% amino acid identity to the human and murine mdr P-glycoproteins. Fly strains bearing disruptions in the homolog in section 49EF have been constructed and implicate this gene in conferring colchicine resistance to the organism. This work sets the foundation for the molecular and genetic analysis of mdr homologs in Drosophila melanogaster.


1991 ◽  
Vol 11 (8) ◽  
pp. 3940-3948 ◽  
Author(s):  
C T Wu ◽  
M Budding ◽  
M S Griffin ◽  
J M Croop

Mammalian multidrug-resistant cell lines, selected for resistance to a single cytotoxic agent, display cross-resistance to a broad spectrum of structurally and functionally unrelated compounds. These cell lines overproduce a membrane protein, the P-glycoprotein, which is encoded by a member(s) of a multigene family, termed mdr or pgp. The amino acid sequence of the P-glycoprotein predicts an energy-dependent transport protein with homology to a large superfamily of proteins which transport a wide variety of substances. This report describes the isolation and characterization of two Drosophila homologs of the mammalian mdr gene. These homologs, located in chromosomal sections 49EF and 65A, encode proteins that share over 40% amino acid identity to the human and murine mdr P-glycoproteins. Fly strains bearing disruptions in the homolog in section 49EF have been constructed and implicate this gene in conferring colchicine resistance to the organism. This work sets the foundation for the molecular and genetic analysis of mdr homologs in Drosophila melanogaster.


2007 ◽  
Vol 30 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Femke M. van de Water ◽  
Johanna M. Boleij ◽  
Janny G.P. Peters ◽  
Frans G.M. Russel ◽  
Rosalinde Masereeuw

1992 ◽  
Vol 50 (6) ◽  
pp. 906-911 ◽  
Author(s):  
C. H. M. Versantvoort ◽  
H. J. Broxterman ◽  
N. Feller ◽  
H. Dekker ◽  
C. M. Kuiper ◽  
...  

Nature ◽  
1985 ◽  
Vol 316 (6031) ◽  
pp. 820-823 ◽  
Author(s):  
Norbert Kartner ◽  
Deanna Evernden-Porelle ◽  
Grace Bradley ◽  
Victor Ling

1989 ◽  
Vol 9 (9) ◽  
pp. 3808-3820 ◽  
Author(s):  
J E Chin ◽  
R Soffir ◽  
K E Noonan ◽  
K Choi ◽  
I B Roninson

The human MDR (P-glycoprotein) gene family is known to include two members, MDR1 and MDR2. The product of the MDR1 gene, which is responsible for resistance to different cytotoxic drugs (multidrug resistance), appears to serve as an energy-dependent efflux pump for various lipophilic compounds. The function of the MDR2 gene remains unknown. We have examined the structure of the human MDR gene family by Southern hybridization of DNA from different multidrug-resistant cell lines with subfragments of MDR1 cDNA and by cloning and sequencing of genomic fragments. We have found no evidence for any other cross-hybridizing MDR genes. The sequence of two exons of the MDR2 gene was determined from genomic clones. Hybridization with single-exon probes showed that the human MDR1 gene is closely related to two genes in mouse and hamster DNA, whereas MDR2 corresponds to one rodent gene. The human MDR locus was mapped by field-inversion gel electrophoresis, and both MDR genes were found to be linked within 330 kilobases. The expression patterns of the human MDR genes were examined by enzymatic amplification of cDNA. In multidrug-resistant cell lines, increased expression of MDR1 mRNA was paralleled by a smaller increase in the levels of MDR2 mRNA. In normal human tissues, MDR2 was coexpressed with MDR1 in the liver, kidney, adrenal gland, and spleen. MDR1 expression was also detected in colon, lung, stomach, esophagus, muscle, breast, and bladder.


1994 ◽  
Vol 56 (5) ◽  
pp. 749-754 ◽  
Author(s):  
Catherine Muller ◽  
Jean-Denis Bailly ◽  
Françoise Goubin ◽  
Judith Laredo ◽  
Jean-Pierre Jaffrézou ◽  
...  

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