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J Biol Chem. 2002 Aug 9;277(32):28656-62. Epub 2002 May 30.

Thyroid hormone receptor alpha 1 regulates expression of the Na+/H+ exchanger (NHE1).

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Department of Biochemistry, Faculty of Medicine, Canadian Institute of Health Research Membrane Protein Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.


In this paper we examine the role of thyroid hormone in regulating expression of the Na+/H+ exchanger. Thyroid hormone has been reported to regulate the activity of the Na+/H+ exchanger messenger RNA in some cell types. Treatment of cardiac myocytes with 3,5',3'-triiodothyronine results in an increased expression of Na+/H+ exchanger protein. Also, compared with euthyroid animals, hypothyroid rats express decreased amounts of the Na+/H+ exchanger protein. To examine the mechanisms involved in regulating expression of the Na+/H+ exchanger, we have characterized the regulation of a distal element of the NHE1 promoter by the thyroid hormone receptor. We have previously shown that a -1085/-800 nucleotide (nt) region of the promoter is a modular element with a -841/-800 nt activating element. Using electrophoretic mobility shift assay, we show that this element interacts with thyroid hormone receptor TRalpha(1), a nuclear hormone receptor. The addition of exogenous TRalpha increased transcriptional activity of the -841/-800 nt element of the Na+/H+ exchanger promoter. We show that TRalpha binds to a region on the -841/-800 nt element that is near, but not identical, to the previously identified chicken ovalbumin upstream promoter transcription factor-binding site. Our results are the first demonstration that thyroid hormone and the thyroid hormone receptor TRalpha(1) regulate expression of the Na+/H+ exchanger.

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