Identification of promotor elements involved in adaptive regulation of the taurine transporter gene

Role of cytosolic Ca2+ signaling

Xiaobin Han, A. M. Budreau, R. W. Chesney

Research output: Contribution to journalArticle

Abstract

The renal tubular epithelium adapts to alterations in the sulfur amino acid composition of the diet, a response that has been well characterized using a cell line derived from the proximal tubule of pig kidney (LLC-PK1). However, the signal pathway through which expression of the taurine transporter gene is regulated by the availability of dietary taurine is unknown. It has been shown that taurine regulates myocardial Ca2+ homeostasis through modulation of several key calcium transport systems. Long-term exposure of heart myocytes to taurine decreases nuclear and cytosolic Ca2+ without significantly changing Na+ levels. Changes in cytoplasmic Ca2+ levels are involved in the regulation of a number of mammalian genes. We have found that the Ca2+ signal may play an important role in adaptive regulation of taurine transporter gene expression. Northern blot analysis showed that ionomycin, a calcium ionophore, increased expression of the taurine transporter gene in a dose-dependent manner, and taurine uptake by LLC-PK1 cells was enhanced after exposing the cells to ionomycin for 48 h. Chelation of calcium with EGTA inhibited tauirne uptake and blocked adaptive regulation of taurine transporter gene expression. 8-Bromocyclic adenosine 3′,5′-monophosphate had no effect on taurine uptake or transporter gene expression in LLC-PK1 cells. Transient transfection of the 5′-flanking region of a rat taurine transporter gene into LLC-PK1 cells showed that ionomycin increased promoter activity of the gene more than 2-fold as compared with control. Deletion of the sequence from -923 to -563 in the 5′-flanking region of the promoter completely abolished the adaptive regulation, as well as the effect of ionomycin on the promoter activity of the taurine transporter gene. This suggests that at least one cis element located between -923 and -563 of the promoter is involved in the adaptive regulation of taurine transporter gene expression by dietary taurine through cytosolic Ca2+ signaling. These findings suggest several models of Ca2+:taurine interaction at the genomic level.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Jan 1 1999

Fingerprint

Taurine
Genes
Ionomycin
LLC-PK1 Cells
Gene expression
Gene Expression
5' Flanking Region
Calcium
Sulfur Amino Acids
Proximal Kidney Tubule
Calcium Ionophores
Sequence Deletion
Egtazic Acid
Nutrition
Chelation
taurine transporter
Northern Blotting
Adenosine
Muscle Cells
Transfection

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Identification of promotor elements involved in adaptive regulation of the taurine transporter gene : Role of cytosolic Ca2+ signaling. / Han, Xiaobin; Budreau, A. M.; Chesney, R. W.

In: Journal of Investigative Medicine, Vol. 47, No. 2, 01.01.1999.

Research output: Contribution to journalArticle

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