Structure and Hormone Responsiveness of the Gene Encoding the α -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel
| Autor: | Harry Robert Bremner, Bijan Rafii, Hugh O'Brodovich, Gail Otulakowski |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pulmonary and Respiratory Medicine
Untranslated region Epithelial sodium channel Gene isoform DNA Complementary Transcription Genetic Clinical Biochemistry Biology Sodium Channels Primer extension Cell Line Exon Rapid amplification of cDNA ends Genes Reporter Animals Humans Coding region Amino Acid Sequence RNA Messenger Cloning Molecular Rats Wistar Epithelial Sodium Channels Promoter Regions Genetic Molecular Biology G alpha subunit Base Sequence Sequence Homology Amino Acid Exons Cell Biology Molecular biology Introns Rats COS Cells |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 20:1028-1040 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.20.5.3382 |
| Popis: | The rat amiloride-sensitive epithelial sodium channel (rENaC) is the rate-limiting step for vectorial transport of Na+ across tight epithelia. The complex is composed of three subunits, alpha, beta, and gamma. Expression of the subunits has been shown to be tissue-specific and developmentally and hormonally regulated. To study mechanisms involved in transcriptional regulation of alpharENaC, we determined the genomic organization of the alpharENaC gene. By 5' rapid amplification of cDNA ends and primer extension, two transcriptional start sites were detected 453 base pairs (bp) apart, resulting in alternative 5' untranslated region (UTR) lengths of 515 or 62 bp. The longer 5' UTR is more prevalent in fetal lung than in adult lung or kidney. The 5' untranslated and coding regions are contained within 12 exons, with the translation start site located within the first exon. Sequence analysis of approximately 1,500 bp of 5' flanking DNA identified putative binding sites for transcription factors PEA3, SP1, AP-1, nuclear factor-kappaB, and thyroid and glucocorticoid receptors. alpharENaC promoter-reporter gene constructs produced low levels of reporter gene activity in transiently transfected cells, which could be increased by dexamethasone (DEX) treatment. Tri-iodothyronine treatment alone had no effect but potentiated stimulation by DEX. |
| Databáze: | OpenAIRE |
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