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Myocyte-Specific M-CAT and MEF-1 Elements Regulate G-Protein Gamma 3 Gene (γ3) Expression in Cardiac Myocytes

McWhinney, Charlene; Robishaw, Janet D.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em /07/2008 Português
Relevância na Pesquisa
Little is known regarding the mechanisms that control the expression of G-protein α, β, and γ subtypes. We have previously shown that the G-protein γ3 gene is expressed in the heart, brain, lung, spleen, kidney, muscle, and testis in mice. We have also reported that the G-protein γ3 subunit is expressed in rat cardiac myocytes, but not in cardiac fibroblasts. Other studies have shown that the γ3 subunit couples to the angiotensin A1A receptor in portal vein myocytes, and has been shown to mediate β-adrenergic desensitization in cardiac myocytes treated with atorvastatin. In the present study, we evaluated G-protein γ3 promoter-luciferase reporter constructs in primary myocytes to identify key regulatory promoter regions. We identified two important regions of the promoter (upstream promoter region [UPR] and downstream promoter region [DPR]), which are required for expression in cardiac myocytes. We observed that removal of 48 bp in the UPR diminished gene transcription by 75%, and that the UPR contains consensus elements for myocyte-specific M-CAT and myocyte enhancer factor 1 (MEF-1) elements. The UPR and DPR share transcription factor elements for myocyte-specific M-CAT element. We observed that cardiac myocyte proteins bind to γ3 oligonucleotides containing transcription factor elements for myocyte-specific M-CAT and MEF-1. Myocyte-specific M-CAT proteins were supershifted with transcriptional enhancer factor-1 (TEF-1) antibodies binding to the γ3 M-CAT element...