Thyroid hormone receptor alpha 1 regulates expression of the Na+/H+ exchanger (NHE1).
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.
Li
Xiuju
X
Department of Biochemistry, Faculty of Medicine, Canadian Institute of Health Research Membrane Protein Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Misik
Angelika J
AJ
Rieder
Carmen V
CV
Solaro
R John
RJ
Lowen
Anice
A
Fliegel
Larry
L
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D017930:Genes, Reporter; D015151:Immunoblotting; D051379:Mice; D009206:Myocardium / Q000166:cytology; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D011988:Receptors, Thyroid Hormone; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1