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...
Ausführliche Beschreibung
Autor*in: |
Sarojini Balkrishna [verfasserIn] Angelika Bröer [verfasserIn] Scott M. Welford [verfasserIn] Maria Hatzoglou [verfasserIn] Stefan Bröer [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2014 |
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Übergeordnetes Werk: |
In: Cellular Physiology and Biochemistry - Cell Physiol Biochem Press GmbH & Co KG, 2002, 33(2014), 5, Seite 1591-1606 |
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Übergeordnetes Werk: |
volume:33 ; year:2014 ; number:5 ; pages:1591-1606 |
Links: |
Link aufrufen |
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DOI / URN: |
10.1159/000358722 |
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Katalog-ID: |
DOAJ079541135 |
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520 | |a 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. | ||
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700 | 0 | |a Stefan Bröer |e verfasserin |4 aut | |
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10.1159/000358722 doi (DE-627)DOAJ079541135 (DE-599)DOAJ89f8c7f469e84bc38b3c6b29b36b7a81 DE-627 ger DE-627 rakwb eng QP1-981 QD415-436 Sarojini Balkrishna verfasserin aut Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Amino acid transport SN1 Promoter methylation Gene regulation Physiology Biochemistry Angelika Bröer verfasserin aut Scott M. Welford verfasserin aut Maria Hatzoglou verfasserin aut Stefan Bröer verfasserin aut In Cellular Physiology and Biochemistry Cell Physiol Biochem Press GmbH & Co KG, 2002 33(2014), 5, Seite 1591-1606 (DE-627)300189702 (DE-600)1482056-0 14219778 nnns volume:33 year:2014 number:5 pages:1591-1606 https://doi.org/10.1159/000358722 kostenfrei https://doaj.org/article/89f8c7f469e84bc38b3c6b29b36b7a81 kostenfrei http://www.karger.com/Article/FullText/358722 kostenfrei https://doaj.org/toc/1015-8987 Journal toc kostenfrei https://doaj.org/toc/1421-9778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2153 GBV_ILN_2885 GBV_ILN_2886 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 33 2014 5 1591-1606 |
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10.1159/000358722 doi (DE-627)DOAJ079541135 (DE-599)DOAJ89f8c7f469e84bc38b3c6b29b36b7a81 DE-627 ger DE-627 rakwb eng QP1-981 QD415-436 Sarojini Balkrishna verfasserin aut Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Amino acid transport SN1 Promoter methylation Gene regulation Physiology Biochemistry Angelika Bröer verfasserin aut Scott M. Welford verfasserin aut Maria Hatzoglou verfasserin aut Stefan Bröer verfasserin aut In Cellular Physiology and Biochemistry Cell Physiol Biochem Press GmbH & Co KG, 2002 33(2014), 5, Seite 1591-1606 (DE-627)300189702 (DE-600)1482056-0 14219778 nnns volume:33 year:2014 number:5 pages:1591-1606 https://doi.org/10.1159/000358722 kostenfrei https://doaj.org/article/89f8c7f469e84bc38b3c6b29b36b7a81 kostenfrei http://www.karger.com/Article/FullText/358722 kostenfrei https://doaj.org/toc/1015-8987 Journal toc kostenfrei https://doaj.org/toc/1421-9778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2153 GBV_ILN_2885 GBV_ILN_2886 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 33 2014 5 1591-1606 |
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10.1159/000358722 doi (DE-627)DOAJ079541135 (DE-599)DOAJ89f8c7f469e84bc38b3c6b29b36b7a81 DE-627 ger DE-627 rakwb eng QP1-981 QD415-436 Sarojini Balkrishna verfasserin aut Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Amino acid transport SN1 Promoter methylation Gene regulation Physiology Biochemistry Angelika Bröer verfasserin aut Scott M. Welford verfasserin aut Maria Hatzoglou verfasserin aut Stefan Bröer verfasserin aut In Cellular Physiology and Biochemistry Cell Physiol Biochem Press GmbH & Co KG, 2002 33(2014), 5, Seite 1591-1606 (DE-627)300189702 (DE-600)1482056-0 14219778 nnns volume:33 year:2014 number:5 pages:1591-1606 https://doi.org/10.1159/000358722 kostenfrei https://doaj.org/article/89f8c7f469e84bc38b3c6b29b36b7a81 kostenfrei http://www.karger.com/Article/FullText/358722 kostenfrei https://doaj.org/toc/1015-8987 Journal toc kostenfrei https://doaj.org/toc/1421-9778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2153 GBV_ILN_2885 GBV_ILN_2886 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 33 2014 5 1591-1606 |
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10.1159/000358722 doi (DE-627)DOAJ079541135 (DE-599)DOAJ89f8c7f469e84bc38b3c6b29b36b7a81 DE-627 ger DE-627 rakwb eng QP1-981 QD415-436 Sarojini Balkrishna verfasserin aut Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Amino acid transport SN1 Promoter methylation Gene regulation Physiology Biochemistry Angelika Bröer verfasserin aut Scott M. Welford verfasserin aut Maria Hatzoglou verfasserin aut Stefan Bröer verfasserin aut In Cellular Physiology and Biochemistry Cell Physiol Biochem Press GmbH & Co KG, 2002 33(2014), 5, Seite 1591-1606 (DE-627)300189702 (DE-600)1482056-0 14219778 nnns volume:33 year:2014 number:5 pages:1591-1606 https://doi.org/10.1159/000358722 kostenfrei https://doaj.org/article/89f8c7f469e84bc38b3c6b29b36b7a81 kostenfrei http://www.karger.com/Article/FullText/358722 kostenfrei https://doaj.org/toc/1015-8987 Journal toc kostenfrei https://doaj.org/toc/1421-9778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2153 GBV_ILN_2885 GBV_ILN_2886 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 33 2014 5 1591-1606 |
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10.1159/000358722 doi (DE-627)DOAJ079541135 (DE-599)DOAJ89f8c7f469e84bc38b3c6b29b36b7a81 DE-627 ger DE-627 rakwb eng QP1-981 QD415-436 Sarojini Balkrishna verfasserin aut Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Amino acid transport SN1 Promoter methylation Gene regulation Physiology Biochemistry Angelika Bröer verfasserin aut Scott M. Welford verfasserin aut Maria Hatzoglou verfasserin aut Stefan Bröer verfasserin aut In Cellular Physiology and Biochemistry Cell Physiol Biochem Press GmbH & Co KG, 2002 33(2014), 5, Seite 1591-1606 (DE-627)300189702 (DE-600)1482056-0 14219778 nnns volume:33 year:2014 number:5 pages:1591-1606 https://doi.org/10.1159/000358722 kostenfrei https://doaj.org/article/89f8c7f469e84bc38b3c6b29b36b7a81 kostenfrei http://www.karger.com/Article/FullText/358722 kostenfrei https://doaj.org/toc/1015-8987 Journal toc kostenfrei https://doaj.org/toc/1421-9778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2153 GBV_ILN_2885 GBV_ILN_2886 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 33 2014 5 1591-1606 |
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Sarojini Balkrishna misc QP1-981 misc QD415-436 misc Amino acid transport misc SN1 misc Promoter methylation misc Gene regulation misc Physiology misc Biochemistry Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression |
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Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression |
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Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression |
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. |
abstractGer |
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_unstemmed |
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. |
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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. 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