Putative P-glycoprotein expression in arsenite-resistant Leishmania donovani down-regulated by verapamil

被引:25
作者
Kaur, J [1 ]
Dey, CS [1 ]
机构
[1] NIPER, Dept Biotechnol, Punjab 160062, India
关键词
arsenite resistance; P-glycoprotein; verapamil; L; donovani;
D O I
10.1006/bbrc.2000.2680
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Western immunoblots of whole cell lysate and crude membrane extract of an in vitro selected sodium m-arsenite-resistant L. donovani strain revealed a 230-kDa protein identified by an anti-P-glycoprotein (Pgp) antibody. Immunofluorescence microscopy, using the same antibody, detected putative Pgp on resistant parasites. Overexpression of the putative Pgp was downregulated by verapamil. These results provided, possibly, the first evidence that (i) overexpression of Pgp-like protein occurs in arsenite-resistant Leishmania that are cross-resistant to structurally and functionally unrelated drugs and (ii) verapamil regulates drug sensitivity possibly by down-regulating Pgp expression in the arsenite-resistant Leishmania. (C) 2000 Academic Press.
引用
收藏
页码:615 / 619
页数:5
相关论文
共 29 条
[1]   PARTIAL-PURIFICATION AND RECONSTITUTION OF THE HUMAN MULTIDRUG-RESISTANCE PUMP - CHARACTERIZATION OF THE DRUG-STIMULATABLE ATP HYDROLYSIS [J].
AMBUDKAR, SV ;
LELONG, IH ;
ZHANG, JP ;
CARDARELLI, CO ;
GOTTESMAN, MM ;
PASTAN, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (18) :8472-8476
[2]  
BORST P, 1995, ANNU REV MICROBIOL, V49, P427, DOI 10.1146/annurev.mi.49.100195.002235
[3]  
CALLAHAN HL, 1991, J BIOL CHEM, V266, P18427
[4]   THE PGPA GENE OF LEISHMANIA-MAJOR MEDIATES ANTIMONY (SBIII) RESISTANCE BY DECREASING INFLUX AND NOT BY INCREASING EFFLUX [J].
CALLAHAN, HL ;
ROBERTS, WL ;
RAINEY, PM ;
BEVERLEY, SM .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1994, 68 (01) :145-149
[5]  
CHIN KV, 1990, J BIOL CHEM, V265, P221
[6]   Altered drug membrane permeability in a multidrug resistant Leishmania tropica line [J].
Chiquero, MJ ;
PerezVictoria, J ;
OValle, F ;
GonzalezRos, JM ;
delMoral, RG ;
Ferragut, JA ;
Castanys, S ;
Gamarro, F .
BIOCHEMICAL PHARMACOLOGY, 1998, 55 (02) :131-139
[7]   CLONING AND FUNCTIONAL-ANALYSIS OF AN EXTRACHROMOSOMALLY AMPLIFIED MULTIDRUG RESISTANCE-LIKE GENE IN LEISHMANIA-ENRIETTII [J].
CHOW, LMC ;
WONG, AKC ;
ULLMAN, B ;
WIRTH, DF .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1993, 60 (02) :195-208
[8]  
CORNWELL MM, 1987, J BIOL CHEM, V262, P2166
[9]   An ATP-dependent As(III)-glutathione transport system in membrane vesicles of Leishmania tarentolae [J].
Dey, S ;
Ouellette, M ;
Lightbody, J ;
Papadopoulou, B ;
Rosen, BP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (05) :2192-2197
[10]   HIGH-LEVEL ARSENITE RESISTANCE IN LEISHMANIA-TARENTOLAE IS MEDIATED BY AN ACTIVE EXTRUSION SYSTEM [J].
DEY, S ;
PAPADOPOULOU, B ;
HAIMEUR, A ;
ROY, G ;
GRONDIN, K ;
DOU, D ;
ROSEN, BP ;
OUELLETTE, M .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1994, 67 (01) :49-57