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

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