ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats
Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are e...
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| Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2010-07, Vol.299 (1), p.G228-G235 |
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| container_title | American journal of physiology: Gastrointestinal and liver physiology |
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| creator | Coy, Donna J Wooton-Kee, Clavia R Yan, Baoxiang Sabeva, Nadezhda Su, Kai Graf, Gregory Vore, Mary |
| description | Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. We investigated the expression of these transporters and secretion of their substrates in female control and lactating Sprague Dawley rats and C57BL/6 mice. Expression of Abcg5/Abcg8 mRNA was decreased by 97 and 60% by midlactation in rats and mice, respectively; protein levels of Abcg8 were below detection limits in lactating rats. Mdr2 mRNA expression was decreased in lactating rats and mice by 47 and 59%, respectively. Despite these changes in transporter expression, basal concentrations of cholesterol and phospholipid in bile were unchanged in rats and mice, whereas increased Bsep mRNA expression in early lactation coincided with an increased basal biliary bile acid concentration in lactating mice. Following taurocholate infusion, coupling of phospholipid and taurocholate secretion in bile of lactating mice was significantly impaired relative to control mice, with no significant changes in maximal secretion of cholesterol or bile acids. In rats, taurocholate infusion revealed a significantly impaired coupling of cholesterol to taurocholate secretion in bile in lactating vs. control animals. These data reveal marked utilization of an Abcg5/Abcg8-independent mechanism for basal biliary cholesterol secretion in rats during lactation, but a dependence on Abcg5/g8 for maximal biliary cholesterol secretion. |
| doi_str_mv | 10.1152/ajpgi.00502.2009 |
| format | Article |
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ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. We investigated the expression of these transporters and secretion of their substrates in female control and lactating Sprague Dawley rats and C57BL/6 mice. Expression of Abcg5/Abcg8 mRNA was decreased by 97 and 60% by midlactation in rats and mice, respectively; protein levels of Abcg8 were below detection limits in lactating rats. Mdr2 mRNA expression was decreased in lactating rats and mice by 47 and 59%, respectively. Despite these changes in transporter expression, basal concentrations of cholesterol and phospholipid in bile were unchanged in rats and mice, whereas increased Bsep mRNA expression in early lactation coincided with an increased basal biliary bile acid concentration in lactating mice. Following taurocholate infusion, coupling of phospholipid and taurocholate secretion in bile of lactating mice was significantly impaired relative to control mice, with no significant changes in maximal secretion of cholesterol or bile acids. In rats, taurocholate infusion revealed a significantly impaired coupling of cholesterol to taurocholate secretion in bile in lactating vs. control animals. These data reveal marked utilization of an Abcg5/Abcg8-independent mechanism for basal biliary cholesterol secretion in rats during lactation, but a dependence on Abcg5/g8 for maximal biliary cholesterol secretion.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.00502.2009</identifier><identifier>PMID: 20413720</identifier><identifier>CODEN: APGPDF</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Adenosine triphosphatase ; Animals ; ATP Binding Cassette Transporter, Subfamily B - metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 5 ; ATP Binding Cassette Transporter, Subfamily G, Member 8 ; ATP-Binding Cassette Sub-Family B Member 4 ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Bile ; Bile - metabolism ; Biological Transport ; Breastfeeding & lactation ; Cholesterol ; Cholesterol - metabolism ; Female ; Infusions, Intravenous ; Lactation - metabolism ; Lipoproteins - genetics ; Lipoproteins - metabolism ; Liver - metabolism ; Liver and Biliary Tract ; Mice ; Mice, Inbred C57BL ; Micelles ; Phospholipids - metabolism ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - metabolism ; Rodents ; Species Specificity ; Taurocholic Acid - administration & dosage ; Taurocholic Acid - metabolism ; Time Factors</subject><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2010-07, Vol.299 (1), p.G228-G235</ispartof><rights>Copyright American Physiological Society Jul 2010</rights><rights>Copyright © 2010 the American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-427e93cfbe5532b65471db2d26d1a17a38a42faea298f91f887c709c74d5665e3</citedby><cites>FETCH-LOGICAL-c422t-427e93cfbe5532b65471db2d26d1a17a38a42faea298f91f887c709c74d5665e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20413720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coy, Donna J</creatorcontrib><creatorcontrib>Wooton-Kee, Clavia R</creatorcontrib><creatorcontrib>Yan, Baoxiang</creatorcontrib><creatorcontrib>Sabeva, Nadezhda</creatorcontrib><creatorcontrib>Su, Kai</creatorcontrib><creatorcontrib>Graf, Gregory</creatorcontrib><creatorcontrib>Vore, Mary</creatorcontrib><title>ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. We investigated the expression of these transporters and secretion of their substrates in female control and lactating Sprague Dawley rats and C57BL/6 mice. Expression of Abcg5/Abcg8 mRNA was decreased by 97 and 60% by midlactation in rats and mice, respectively; protein levels of Abcg8 were below detection limits in lactating rats. Mdr2 mRNA expression was decreased in lactating rats and mice by 47 and 59%, respectively. Despite these changes in transporter expression, basal concentrations of cholesterol and phospholipid in bile were unchanged in rats and mice, whereas increased Bsep mRNA expression in early lactation coincided with an increased basal biliary bile acid concentration in lactating mice. Following taurocholate infusion, coupling of phospholipid and taurocholate secretion in bile of lactating mice was significantly impaired relative to control mice, with no significant changes in maximal secretion of cholesterol or bile acids. In rats, taurocholate infusion revealed a significantly impaired coupling of cholesterol to taurocholate secretion in bile in lactating vs. control animals. These data reveal marked utilization of an Abcg5/Abcg8-independent mechanism for basal biliary cholesterol secretion in rats during lactation, but a dependence on Abcg5/g8 for maximal biliary cholesterol secretion.</description><subject>Adenosine triphosphatase</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter, Subfamily B - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 5</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 8</subject><subject>ATP-Binding Cassette Sub-Family B Member 4</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Bile</subject><subject>Bile - metabolism</subject><subject>Biological Transport</subject><subject>Breastfeeding & lactation</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Female</subject><subject>Infusions, Intravenous</subject><subject>Lactation - metabolism</subject><subject>Lipoproteins - genetics</subject><subject>Lipoproteins - metabolism</subject><subject>Liver - metabolism</subject><subject>Liver and Biliary Tract</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Micelles</subject><subject>Phospholipids - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Species Specificity</subject><subject>Taurocholic Acid - administration & dosage</subject><subject>Taurocholic Acid - metabolism</subject><subject>Time Factors</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1PwzAMxSMEYmNw54Qq7t0cN2naC9KYYCBN4gLnKE3TLVPXlLRD8N-TfYDg4kjx8_PPj5BrCmNKOU7Uul3aMQAHHCNAfkKG4Rtjypk4JUOgeRLTjIsBuei6NQQhUnpOBgiMJgJhSObT-9mcT3Y1i21TmtaE0vRRYWur_FekV642XW-8qyPzqb3prWsi20S10r3qbbOMvOq7S3JWqbozV8d3RN4eH15nT_HiZf48my5izRD7mKEweaKrwnCeYJEGTloWWGJaUkWFSjLFsFJGYZ5VOa2yTGgBuRas5GnKTTIidwffdltsTKkDqle1bL3dBFrplJX_O41dyaX7kJiHm4EFg9ujgXfv23CZXLutbwKz5MAECxsxiOAg0t51nTfV7wIKcpe83Ccv98nLXfJh5OYv2O_AT9TJN3Vxf7w</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Coy, Donna J</creator><creator>Wooton-Kee, Clavia R</creator><creator>Yan, Baoxiang</creator><creator>Sabeva, Nadezhda</creator><creator>Su, Kai</creator><creator>Graf, Gregory</creator><creator>Vore, Mary</creator><general>American Physiological Society</general><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>5PM</scope></search><sort><creationdate>20100701</creationdate><title>ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats</title><author>Coy, Donna J ; Wooton-Kee, Clavia R ; Yan, Baoxiang ; Sabeva, Nadezhda ; Su, Kai ; Graf, Gregory ; Vore, Mary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-427e93cfbe5532b65471db2d26d1a17a38a42faea298f91f887c709c74d5665e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenosine triphosphatase</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter, Subfamily B - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 5</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 8</topic><topic>ATP-Binding Cassette Sub-Family B Member 4</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Bile</topic><topic>Bile - metabolism</topic><topic>Biological Transport</topic><topic>Breastfeeding & lactation</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Female</topic><topic>Infusions, Intravenous</topic><topic>Lactation - metabolism</topic><topic>Lipoproteins - genetics</topic><topic>Lipoproteins - metabolism</topic><topic>Liver - metabolism</topic><topic>Liver and Biliary Tract</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Micelles</topic><topic>Phospholipids - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Species Specificity</topic><topic>Taurocholic Acid - administration & dosage</topic><topic>Taurocholic Acid - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coy, Donna J</creatorcontrib><creatorcontrib>Wooton-Kee, Clavia R</creatorcontrib><creatorcontrib>Yan, Baoxiang</creatorcontrib><creatorcontrib>Sabeva, Nadezhda</creatorcontrib><creatorcontrib>Su, Kai</creatorcontrib><creatorcontrib>Graf, Gregory</creatorcontrib><creatorcontrib>Vore, Mary</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coy, Donna J</au><au>Wooton-Kee, Clavia R</au><au>Yan, Baoxiang</au><au>Sabeva, Nadezhda</au><au>Su, Kai</au><au>Graf, Gregory</au><au>Vore, Mary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>299</volume><issue>1</issue><spage>G228</spage><epage>G235</epage><pages>G228-G235</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><coden>APGPDF</coden><abstract>Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. We investigated the expression of these transporters and secretion of their substrates in female control and lactating Sprague Dawley rats and C57BL/6 mice. Expression of Abcg5/Abcg8 mRNA was decreased by 97 and 60% by midlactation in rats and mice, respectively; protein levels of Abcg8 were below detection limits in lactating rats. Mdr2 mRNA expression was decreased in lactating rats and mice by 47 and 59%, respectively. Despite these changes in transporter expression, basal concentrations of cholesterol and phospholipid in bile were unchanged in rats and mice, whereas increased Bsep mRNA expression in early lactation coincided with an increased basal biliary bile acid concentration in lactating mice. Following taurocholate infusion, coupling of phospholipid and taurocholate secretion in bile of lactating mice was significantly impaired relative to control mice, with no significant changes in maximal secretion of cholesterol or bile acids. In rats, taurocholate infusion revealed a significantly impaired coupling of cholesterol to taurocholate secretion in bile in lactating vs. control animals. These data reveal marked utilization of an Abcg5/Abcg8-independent mechanism for basal biliary cholesterol secretion in rats during lactation, but a dependence on Abcg5/g8 for maximal biliary cholesterol secretion.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>20413720</pmid><doi>10.1152/ajpgi.00502.2009</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine triphosphatase Animals ATP Binding Cassette Transporter, Subfamily B - metabolism ATP Binding Cassette Transporter, Subfamily G, Member 5 ATP Binding Cassette Transporter, Subfamily G, Member 8 ATP-Binding Cassette Sub-Family B Member 4 ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Bile Bile - metabolism Biological Transport Breastfeeding & lactation Cholesterol Cholesterol - metabolism Female Infusions, Intravenous Lactation - metabolism Lipoproteins - genetics Lipoproteins - metabolism Liver - metabolism Liver and Biliary Tract Mice Mice, Inbred C57BL Micelles Phospholipids - metabolism Rats Rats, Sprague-Dawley RNA, Messenger - metabolism Rodents Species Specificity Taurocholic Acid - administration & dosage Taurocholic Acid - metabolism Time Factors |
| title | ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats |
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