Thyroid Hormone Receptor α1 Regulates Expression of the Na+/H+ Exchanger (NHE1)

• Published in: The Journal of biological chemistry Vol. 277; no. 32; p. 28656
• Main Authors: Xiuju Li, Angelika J. Misik, Carmen V. Rieder, R. John Solaro, Anice Lowen, Larry Fliegel
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 09.08.2002
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M203221200

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 TRα 1 , a nuclear hormone receptor. The addition of exogenous TRα increased transcriptional activity of the −841/−800 nt element of the Na + /H + exchanger promoter. We show that TRα 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 TRα 1 regulate expression of the Na + /H + exchanger.