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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.

SUBMITTER: Balkrishna S

PROVIDER: S-EPMC4424794 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated by a different mechanism than tissue-specific expression.

Balkrishna Sarojini S Bröer Angelika A Welford Scott M SM Hatzoglou Maria M Bröer Stefan S

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20140516 5

<h4>Background</h4>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.<h4>Methods</h4>Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values.<h4>Results</h4>Up-regulatio ...[more]

PMID: 24854847

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Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated by a different mechanism than tissue-specific expression.

Publications

Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated by a different mechanism than tissue-specific expression.

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