THE P-GLYCOPROTEIN-RELATED GENE FAMILY IN LEISHMANIA

被引:59
作者
LEGARE, D
HETTEMA, E
OUELLETTE, M
机构
[1] CHUL,CTR RECH,SERV INFECTIOL,ST FOY G1V 4G2,PQ,CANADA
[2] NETHERLANDS CANC INST,DIV MOLEC BIOL,1066 CX AMSTERDAM,NETHERLANDS
[3] UNIV LAVAL,DEPT MICROBIOL,ST FOY G1V 4G2,PQ,CANADA
基金
加拿大自然科学与工程研究理事会;
关键词
LEISHMANIA; P-GLYCOPROTEIN; DRUG RESISTANCE; GENE FAMILY;
D O I
10.1016/0166-6851(94)00156-1
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
P-glycoprotein gene amplification has been described in several drug-resistant parasitic protozoa. The first P-glycoprotein related gene described in Leishmania was ItpgpA, a gene frequently amplified in arsenite resistant Leishmania. Hybridization experiments indicated that ItpgpA was part of a gene family. In addition to ItpgpA, four novel genes were cloned that are present in two loci: ItpgpB and ItpgpC tandemly linked to ItpgpA on a 800-kb chromosome; and ItpgpD and ItpgpE closely linked on a chromosome ranging from 950 kb to 1400 kb, depending on the Leishmania species. Another P-glycoprotein gene, homologous to the more recently described Idmdr1, was linked to ItpgpD and ItpgpE. Nucleotide sequencing of ItpgpB and ItpgpE revealed that the Leishmania P-glycoprotein-related genes have diverged considerably from the main branch of P-glycoproteins and are more homologous to the recently described multidrug resistance-associated protein found in multidrug-resistant human lung cancer cell lines. Cross-resistance studies and gene transfection experiments indicated that under the conditions tested only ItpgpA and Idmdr1 are involved in resistance to arsenite and antimonials or hydrophobic drugs such as vinblastine respectively.
引用
收藏
页码:81 / 91
页数:11
相关论文
共 34 条
[1]  
BORST P, 1992, P BRISTOL MYERS SQUI, V14, P11
[2]  
CALLAHAN HL, 1991, J BIOL CHEM, V266, P18427
[3]   INTERNAL DUPLICATION AND HOMOLOGY WITH BACTERIAL TRANSPORT PROTEINS IN THE MDR1 (P-GLYCOPROTEIN) GENE FROM MULTIDRUG-RESISTANT HUMAN-CELLS [J].
CHEN, CJ ;
CHIN, JE ;
UEDA, K ;
CLARK, DP ;
PASTAN, I ;
GOTTESMAN, MM ;
RONINSON, IB .
CELL, 1986, 47 (03) :381-389
[4]   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
[5]   OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].
COLE, SPC ;
BHARDWAJ, G ;
GERLACH, JH ;
MACKIE, JE ;
GRANT, CE ;
ALMQUIST, KC ;
STEWART, AJ ;
KURZ, EU ;
DUNCAN, AMV ;
DEELEY, RG .
SCIENCE, 1992, 258 (5088) :1650-1654
[6]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395
[7]  
DOIGE CA, 1993, ANNU REV MICROBIOL, V47, P291, DOI 10.1146/annurev.mi.47.100193.001451
[8]   A TECHNIQUE FOR RADIOLABELING DNA RESTRICTION ENDONUCLEASE FRAGMENTS TO HIGH SPECIFIC ACTIVITY [J].
FEINBERG, AP ;
VOGELSTEIN, B .
ANALYTICAL BIOCHEMISTRY, 1983, 132 (01) :6-13
[9]   P-GLYCOPROTEIN OVEREXPRESSION IN METHOTREXATE-RESISTANT LEISHMANIA-TROPICA [J].
GAMARRO, F ;
CHIQUERO, MJ ;
AMADOR, MV ;
LEGARE, D ;
OUELLETTE, M ;
CASTANYS, S .
BIOCHEMICAL PHARMACOLOGY, 1994, 47 (11) :1939-1947
[10]   KARYOTYPE ANALYSIS OF LEISHMANIA SPECIES AND ITS USE IN CLASSIFICATION AND CLINICAL-DIAGNOSIS [J].
GIANNINI, SH ;
SCHITTINI, M ;
KEITHLY, JS ;
WARBURTON, PW ;
CANTOR, CR ;
VANDERPLOEG, LHT .
SCIENCE, 1986, 232 (4751) :762-765