Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression
Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammon...
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| Veröffentlicht in: | Cellular physiology and biochemistry 2014-01, Vol.33 (5), p.1591-1606 |
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| container_title | Cellular physiology and biochemistry |
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| creator | Balkrishna, Sarojini Bröer, Angelika Welford, Scott M. Hatzoglou, Maria Bröer, Stefan |
| description | Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene. |
| doi_str_mv | 10.1159/000358722 |
| format | Article |
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Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000358722</identifier><identifier>PMID: 24854847</identifier><language>eng</language><publisher>Basel, Switzerland: Cell Physiol Biochem Press GmbH & Co KG</publisher><subject>Acidosis - genetics ; Acidosis - metabolism ; Amino acid transport ; Amino Acid Transport Systems, Neutral - biosynthesis ; Amino Acid Transport Systems, Neutral - genetics ; Animals ; Cells, Cultured ; Gene regulation ; HEK293 Cells ; HeLa Cells ; Hep G2 Cells ; Humans ; Hydrogen-Ion Concentration ; Mice ; Organ Specificity - genetics ; Original Paper ; Promoter methylation ; Promoter Regions, Genetic - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; SN1 ; Transcription, Genetic - genetics</subject><ispartof>Cellular physiology and biochemistry, 2014-01, Vol.33 (5), p.1591-1606</ispartof><rights>2014 S. Karger AG, Basel</rights><rights>2014 S. Karger AG, Basel.</rights><rights>Copyright © 2014 S. Karger AG, Basel 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-c946845a66ad4480df7392ae8c850160688620556d5dbff37f9c7b9b026530413</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,864,885,2102,27635,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24854847$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balkrishna, Sarojini</creatorcontrib><creatorcontrib>Bröer, Angelika</creatorcontrib><creatorcontrib>Welford, Scott M.</creatorcontrib><creatorcontrib>Hatzoglou, Maria</creatorcontrib><creatorcontrib>Bröer, Stefan</creatorcontrib><title>Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene.</description><subject>Acidosis - genetics</subject><subject>Acidosis - metabolism</subject><subject>Amino acid transport</subject><subject>Amino Acid Transport Systems, Neutral - biosynthesis</subject><subject>Amino Acid Transport Systems, Neutral - genetics</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Gene regulation</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Mice</subject><subject>Organ Specificity - genetics</subject><subject>Original Paper</subject><subject>Promoter methylation</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>SN1</subject><subject>Transcription, Genetic - genetics</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNpVkktv1DAQxyMEoqVw4I6Qj-0h4PfjgrTqi0oFDrucLduxty5JvLUTRL8BH7suuyxUGmnG45__47Gnad4i-AEhpj5CCAmTAuNnzSGiGLVKCPm8xhCxViopDppXpdzCuhQKv2wOMJWMSioOm9_nvzbZlxLTCFIAl_08mSGOHqyyGcsm5clnsOwdkYaA4-XXxYqcgLM5x3ENFi52qcQCqn3xXTST74C9BwacxRB89uNU8-7GjLEMYKoerGIps2-XG-9iiA78q_66eRFMX_ybnT9qvl-cr04_t9ffLq9OF9etY1hOrVOUS8oM56ajVMIuCKKw8dJJBhGHXEqOIWO8Y50NgYignLDKQswZgRSRo-Zqq9slc6s3OQ4m3-tkov6TSHmtTZ6i672WKkgnAuXKS2rrE1jiuMXKEm6FkY9an7Zam9kOvnO14Wz6J6JPd8Z4o9fpp6YUU6FoFTjeCeR0N_sy6SEW5_vejD7NRaPaMyEcCVjRky3qciol-7Avg6B-nAK9n4LKvv__Xnvy77dX4N0W-GHy2uc9sDv_AMwstb8</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Balkrishna, Sarojini</creator><creator>Bröer, Angelika</creator><creator>Welford, Scott M.</creator><creator>Hatzoglou, Maria</creator><creator>Bröer, Stefan</creator><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</scope><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><scope>DOA</scope></search><sort><creationdate>20140101</creationdate><title>Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression</title><author>Balkrishna, Sarojini ; Bröer, Angelika ; Welford, Scott M. ; Hatzoglou, Maria ; Bröer, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-c946845a66ad4480df7392ae8c850160688620556d5dbff37f9c7b9b026530413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acidosis - genetics</topic><topic>Acidosis - metabolism</topic><topic>Amino acid transport</topic><topic>Amino Acid Transport Systems, Neutral - biosynthesis</topic><topic>Amino Acid Transport Systems, Neutral - genetics</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Gene regulation</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Mice</topic><topic>Organ Specificity - genetics</topic><topic>Original Paper</topic><topic>Promoter methylation</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>SN1</topic><topic>Transcription, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balkrishna, Sarojini</creatorcontrib><creatorcontrib>Bröer, Angelika</creatorcontrib><creatorcontrib>Welford, Scott M.</creatorcontrib><creatorcontrib>Hatzoglou, Maria</creatorcontrib><creatorcontrib>Bröer, Stefan</creatorcontrib><collection>Karger Open Access</collection><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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balkrishna, Sarojini</au><au>Bröer, Angelika</au><au>Welford, Scott M.</au><au>Hatzoglou, Maria</au><au>Bröer, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>33</volume><issue>5</issue><spage>1591</spage><epage>1606</epage><pages>1591-1606</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene.</abstract><cop>Basel, Switzerland</cop><pub>Cell Physiol Biochem Press GmbH & Co KG</pub><pmid>24854847</pmid><doi>10.1159/000358722</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acidosis - genetics Acidosis - metabolism Amino acid transport Amino Acid Transport Systems, Neutral - biosynthesis Amino Acid Transport Systems, Neutral - genetics Animals Cells, Cultured Gene regulation HEK293 Cells HeLa Cells Hep G2 Cells Humans Hydrogen-Ion Concentration Mice Organ Specificity - genetics Original Paper Promoter methylation Promoter Regions, Genetic - genetics RNA, Messenger - genetics RNA, Messenger - metabolism SN1 Transcription, Genetic - genetics |
| title | Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression |
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