Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues
Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack th...
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| Veröffentlicht in: | Biochemical journal 2002-02, Vol.361 (Pt 3), p.497-503 |
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| description | Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH. |
| doi_str_mv | 10.1042/0264-6021:3610497 |
| format | Article |
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Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/0264-6021:3610497</identifier><identifier>PMID: 11802779</identifier><language>eng</language><publisher>England</publisher><subject>Adenosine Triphosphate - metabolism ; Animals ; Biological Transport ; Blotting, Western ; Cell Line ; Cloning, Molecular ; Cyclic AMP - metabolism ; Dogs ; Glutathione - chemistry ; Glutathione - metabolism ; Glutathione - physiology ; Humans ; Immunoblotting ; Microscopy, Fluorescence ; Multidrug Resistance-Associated Proteins ; Protein Structure, Tertiary ; Purines - chemistry ; Ribosomal Proteins - chemistry ; Transfection ; Tumor Cells, Cultured</subject><ispartof>Biochemical journal, 2002-02, Vol.361 (Pt 3), p.497-503</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-b24aa308fd77c700c02128f463bb550295724bb02d3771474bf6d812e1d390263</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222332/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222332/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11802779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Liqi</creatorcontrib><creatorcontrib>Tan, Theresa M C</creatorcontrib><title>Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cloning, Molecular</subject><subject>Cyclic AMP - metabolism</subject><subject>Dogs</subject><subject>Glutathione - chemistry</subject><subject>Glutathione - metabolism</subject><subject>Glutathione - physiology</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Microscopy, Fluorescence</subject><subject>Multidrug Resistance-Associated Proteins</subject><subject>Protein Structure, Tertiary</subject><subject>Purines - chemistry</subject><subject>Ribosomal Proteins - chemistry</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUUtLAzEYDKJoffwAL5KT6GE1r252PQi1-IIWS9FzyO5m20i6qUlW9Og_N0tLradAvpn55psB4BSjK4wYuUYkZUmKCL6hafzI-Q7oYcZRknGS7YLeZn4ADr1_RwgzxNA-OMA4Q4TzvAd-ptYoaGs4M22QYa5to6BuYJgruGhN0JVrZ9Apr32QTang0tmgIoDBi_F0wq4Hd8Mhu0wWqtIyqAqqujbtV6dYDsYTKJtqmx0sXLZOxx2ykcbOWuWPwV4tjVcn6_cIvD3cvw6fktHL4_NwMEpKmvdDUhAmJUVZXXFecoTKeBbJapbSouj3Ecn7nLCiQKSinMcQWFGnVYaJwhXNYxD0CNyudJdtEd2WqglOGrF0eiHdt7BSi_-TRs_FzH4KTAihlESB87WAsx_ReBAL7UtljGyUbb3gXboZzyIQr4Cls947VW-WYCS64kRXjOiKEeviIuds290fY90U_QXX3pNy</recordid><startdate>20020201</startdate><enddate>20020201</enddate><creator>Lai, Liqi</creator><creator>Tan, Theresa M C</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20020201</creationdate><title>Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues</title><author>Lai, Liqi ; Tan, Theresa M C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-b24aa308fd77c700c02128f463bb550295724bb02d3771474bf6d812e1d390263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cloning, Molecular</topic><topic>Cyclic AMP - metabolism</topic><topic>Dogs</topic><topic>Glutathione - chemistry</topic><topic>Glutathione - metabolism</topic><topic>Glutathione - physiology</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Microscopy, Fluorescence</topic><topic>Multidrug Resistance-Associated Proteins</topic><topic>Protein Structure, Tertiary</topic><topic>Purines - chemistry</topic><topic>Ribosomal Proteins - chemistry</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Liqi</creatorcontrib><creatorcontrib>Tan, Theresa M C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Liqi</au><au>Tan, Theresa M C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>2002-02-01</date><risdate>2002</risdate><volume>361</volume><issue>Pt 3</issue><spage>497</spage><epage>503</epage><pages>497-503</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.</abstract><cop>England</cop><pmid>11802779</pmid><doi>10.1042/0264-6021:3610497</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Triphosphate - metabolism Animals Biological Transport Blotting, Western Cell Line Cloning, Molecular Cyclic AMP - metabolism Dogs Glutathione - chemistry Glutathione - metabolism Glutathione - physiology Humans Immunoblotting Microscopy, Fluorescence Multidrug Resistance-Associated Proteins Protein Structure, Tertiary Purines - chemistry Ribosomal Proteins - chemistry Transfection Tumor Cells, Cultured |
| title | Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues |
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