Characterization of the ATP-dependent LTC(4) transporter in cisplatin-resistant human KB cells

被引：36

作者：

Chuman, Y ^{[1
]}

Chen, ZS ^{[1
]}

Sumizawa, T ^{[1
]}

Furukawa, T ^{[1
]}

Haraguchi, M ^{[1
]}

Takebayashi, Y ^{[1
]}

Niwa, K ^{[1
]}

Yamada, K ^{[1
]}

Aikou, T ^{[1
]}

Akiyama, S ^{[1
]}

机构：

[1] KAGOSHIMA UNIV,FAC MED,DEPT SURG 1,KAGOSHIMA 890,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1996年 / 226卷 / 01期

关键词：

D O I：

10.1006/bbrc.1996.1326

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：

An active efflux pump for cis-diamminedichloroplatinum(II) (cisplatin) has been identified in cisplatin-resistant KCP-4 cells isolated from human epidermoid carcinoma KB-3-1 cells. The adenosine triphosphate(ATP)-dependent transport of leukotriene C-4 (LTC(4)), an endogenous substrate for the glutathione S-conjugate export pump(GS-X pump), has been found in membrane vesicles prepared from KCP-4 cells. Multidrug resistance-associated protein (MRP) has also been identified as an ATP-dependent LTC(4) transporter. To examine whether the GS-X pump expressed in KCP-4 cells is MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC(4) transporting activity of GS-X pump expressed in KCP-4 cells with that of MRP. The level of MRP gene expression in KCP-4 cells was low and similar to that in KB-3-1 cells.,MRP was not detected in membrane vesicles prepared from KB-3-1 and KCP-4 cells by immnunoblot analysis. The ATP-dependent transport of LTC(4) in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 mu M and 0.25 mu M, respectively. [H-3]LTC(4) transport in KCP-4 Vesicles was more inhibited by 2,4-dinitrophenyl-S-glutathione(DNP-SG), bis-(glutathionato)-platinum(II) (GS-platinum) complex and glutathione disulfide(GS-SG) and less by LTD(4) compared with that in C-A120 vesicles. The character of the LTC(4) transporter expressed in KCP-4 vesicles is similar but not identical to that of MRP. Our results suggest that a glutathione S-conjugate export pump which is different from MRP exists in cisplatin-resistant KCP-4 cells. (C) 1996 Academic Press, Inc.

引用

页码：158 / 165

页数：8

共 28 条

[1] ISOLATION AND GENETIC-CHARACTERIZATION OF HUMAN KB-CELL LINES RESISTANT TO MULTIPLE-DRUGS [J].

AKIYAMA, SI ;

FOJO, A ;

HANOVER, JA ;

PASTAN, I ;

GOTTESMAN, MM .

SOMATIC CELL AND MOLECULAR GENETICS, 1985, 11 (02) :117-126

[2] CISPLATIN-RESISTANT CELLS EXPRESS INCREASED LEVELS OF A FACTOR THAT RECOGNIZES DAMAGED DNA [J].

CHU, G ;

CHANG, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (09) :3324-3327

[3]

CLUGSTON CK, 1992, CANCER RES, V52, P6375

[4] 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

[5]

CORNWELL MM, 1986, J BIOL CHEM, V261, P7921

[6] PRELYSOSOMAL DIVERGENCE OF TRANSFERRIN AND EPIDERMAL GROWTH-FACTOR DURING RECEPTOR-MEDIATED ENDOCYTOSIS [J].

DICKSON, RB ;

HANOVER, JA ;

WILLINGHAM, MC ;

PASTAN, I .

BIOCHEMISTRY, 1983, 22 (24) :5667-5674

[7] ACTIVE EFFLUX SYSTEM FOR CISPLATIN IN CISPLATIN-RESISTANT HUMAN KB CELLS [J].

FUJII, R ;

MUTOH, M ;

NIWA, K ;

YAMADA, K ;

AIKOU, T ;

NAKAGAWA, M ;

KUWANO, M ;

AKIYAMA, S .

JAPANESE JOURNAL OF CANCER RESEARCH, 1994, 85 (04) :426-433

[8] ADENOSINE TRIPHOSPHATE-DEPENDENT TRANSPORT OF LEUKOTRIENE C-4 BY MEMBRANE-VESICLES PREPARED FROM CISPLATIN-RESISTANT HUMAN EPIDERMOID CARCINOMA TUMOR-CELLS [J].

FUJII, R ;

MUTOH, M ;

SUMIZAWA, T ;

CHEN, ZS ;

YOSHIMURA, A ;

AKIYAMA, S .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (23) :1781-1784

[9] HIGH-RESISTANCE TO CISPLATIN IN HUMAN OVARIAN-CANCER CELL-LINES IS ASSOCIATED WITH MARKED INCREASE OF GLUTATHIONE SYNTHESIS [J].

GODWIN, AK ;

MEISTER, A ;

ODWYER, PJ ;

HUANG, CS ;

HAMILTON, TC ;

ANDERSON, ME .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3070-3074

[10]

GRANT CE, 1994, CANCER RES, V54, P357

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