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

Sarojini Balkrishna, Angelika Bröer, Scott M. Welford, Maria Hatzoglou, Stefan Bröer

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1591-1606
Number of pages16
JournalCellular Physiology and Biochemistry
Volume33
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

Keywords

  • Amino acid transport
  • Gene regulation
  • Promoter methylation
  • SN1

ASJC Scopus subject areas

  • Physiology

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