Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells
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 C4 (LTC4), an endogenous substrate for the glutathio...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1996-09, Vol.226 (1), p.158-165 |
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| creator | Chuman, Y Chen, Z S Sumizawa, T Furukawa, T Haraguchi, M Takebayashi, Y Niwa, K Yamada, K Aikou, T Akiyama, S |
| description | 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 C4 (LTC4), 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 LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 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 immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 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 LTD4 compared with that in C-A120 vesicles. The character of the LTC4 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. |
| doi_str_mv | 10.1006/bbrc.1996.1326 |
| format | Article |
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The adenosine triphosphate(ATP)-dependent transport of leukotriene C4 (LTC4), 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 LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 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 immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 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 LTD4 compared with that in C-A120 vesicles. The character of the LTC4 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.</description><identifier>ISSN: 0006-291X</identifier><identifier>DOI: 10.1006/bbrc.1996.1326</identifier><identifier>PMID: 8806607</identifier><language>eng</language><publisher>United States</publisher><subject>Adenosine Triphosphate - metabolism ; Amino Acid Sequence ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; ATP-Binding Cassette Transporters - genetics ; Biological Transport ; Cell Membrane - metabolism ; Cisplatin - pharmacology ; Drug Resistance, Neoplasm ; Glutathione - metabolism ; Humans ; Leukotriene C4 - metabolism ; Molecular Sequence Data ; Multidrug Resistance-Associated Proteins ; Osmolar Concentration ; RNA, Messenger - genetics ; Tritium ; Tumor Cells, Cultured ; Verapamil - metabolism</subject><ispartof>Biochemical and biophysical research communications, 1996-09, Vol.226 (1), p.158-165</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8806607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chuman, Y</creatorcontrib><creatorcontrib>Chen, Z S</creatorcontrib><creatorcontrib>Sumizawa, T</creatorcontrib><creatorcontrib>Furukawa, T</creatorcontrib><creatorcontrib>Haraguchi, M</creatorcontrib><creatorcontrib>Takebayashi, Y</creatorcontrib><creatorcontrib>Niwa, K</creatorcontrib><creatorcontrib>Yamada, K</creatorcontrib><creatorcontrib>Aikou, T</creatorcontrib><creatorcontrib>Akiyama, S</creatorcontrib><title>Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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 C4 (LTC4), 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 LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 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 immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 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 LTD4 compared with that in C-A120 vesicles. The character of the LTC4 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.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Amino Acid Sequence</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Biological Transport</subject><subject>Cell Membrane - metabolism</subject><subject>Cisplatin - pharmacology</subject><subject>Drug Resistance, Neoplasm</subject><subject>Glutathione - metabolism</subject><subject>Humans</subject><subject>Leukotriene C4 - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Multidrug Resistance-Associated Proteins</subject><subject>Osmolar Concentration</subject><subject>RNA, Messenger - genetics</subject><subject>Tritium</subject><subject>Tumor Cells, Cultured</subject><subject>Verapamil - metabolism</subject><issn>0006-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNot0E1LxDAQBuAclHVdvXoTcvLWNR9NNjlq8QsX9LCCB6FMk5SNtGlN0oP-eivuaeDlmeFlELqgZE0JkddNE82aai3XlDN5hJZkTgum6fsJOk3pkxBKS6kXaKEUkZJsluij2kMEk130P5D9EPDQ4rx3-Gb3Wlg3umBdyHi7q0qcI4Q0DnHG2AdsfBq7eScU0SWfMsxuP_UQ8PMtNq7r0hk6bqFL7vwwV-jt_m5XPRbbl4en6mZbjJTRXAhLheCGABChrVCygVIQY7kBuhG6NZo6plkLijkBkkvbSEasLpVxrSklX6Gr_7tjHL4ml3Ld-_TXAIIbplRvFGczUzO8PMCp6Z2tx-h7iN_14R38F3B9YJ0</recordid><startdate>19960904</startdate><enddate>19960904</enddate><creator>Chuman, Y</creator><creator>Chen, Z S</creator><creator>Sumizawa, T</creator><creator>Furukawa, T</creator><creator>Haraguchi, M</creator><creator>Takebayashi, Y</creator><creator>Niwa, K</creator><creator>Yamada, K</creator><creator>Aikou, T</creator><creator>Akiyama, S</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19960904</creationdate><title>Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells</title><author>Chuman, Y ; Chen, Z S ; Sumizawa, T ; Furukawa, T ; Haraguchi, M ; Takebayashi, Y ; Niwa, K ; Yamada, K ; Aikou, T ; Akiyama, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p121t-5d1553c0aa059d586ba450cd3ca1759fc91e292fa82e5a636db620d948cefc463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Amino Acid Sequence</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Biological Transport</topic><topic>Cell Membrane - metabolism</topic><topic>Cisplatin - pharmacology</topic><topic>Drug Resistance, Neoplasm</topic><topic>Glutathione - metabolism</topic><topic>Humans</topic><topic>Leukotriene C4 - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Multidrug Resistance-Associated Proteins</topic><topic>Osmolar Concentration</topic><topic>RNA, Messenger - genetics</topic><topic>Tritium</topic><topic>Tumor Cells, Cultured</topic><topic>Verapamil - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chuman, Y</creatorcontrib><creatorcontrib>Chen, Z S</creatorcontrib><creatorcontrib>Sumizawa, T</creatorcontrib><creatorcontrib>Furukawa, T</creatorcontrib><creatorcontrib>Haraguchi, M</creatorcontrib><creatorcontrib>Takebayashi, Y</creatorcontrib><creatorcontrib>Niwa, K</creatorcontrib><creatorcontrib>Yamada, K</creatorcontrib><creatorcontrib>Aikou, T</creatorcontrib><creatorcontrib>Akiyama, S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chuman, Y</au><au>Chen, Z S</au><au>Sumizawa, T</au><au>Furukawa, T</au><au>Haraguchi, M</au><au>Takebayashi, Y</au><au>Niwa, K</au><au>Yamada, K</au><au>Aikou, T</au><au>Akiyama, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1996-09-04</date><risdate>1996</risdate><volume>226</volume><issue>1</issue><spage>158</spage><epage>165</epage><pages>158-165</pages><issn>0006-291X</issn><abstract>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 C4 (LTC4), 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 LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 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 immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 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 LTD4 compared with that in C-A120 vesicles. The character of the LTC4 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.</abstract><cop>United States</cop><pmid>8806607</pmid><doi>10.1006/bbrc.1996.1326</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenosine Triphosphate - metabolism Amino Acid Sequence ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP-Binding Cassette Transporters - genetics Biological Transport Cell Membrane - metabolism Cisplatin - pharmacology Drug Resistance, Neoplasm Glutathione - metabolism Humans Leukotriene C4 - metabolism Molecular Sequence Data Multidrug Resistance-Associated Proteins Osmolar Concentration RNA, Messenger - genetics Tritium Tumor Cells, Cultured Verapamil - metabolism |
| title | Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells |
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