Phenylephrine requires the TATA box to activate transcription of GLUT1 in neonatal rat cardiac myocytes.
Cardiac hypertrophy and heart failure occur in association to alterations in glucose uptake and metabolism. Phenylephrine, among other hypertrophic agonists, has been reported to increase expression of GLUT1 in neonatal rat cardiac myocytes by activating transcription. However, the specific cis- or trans-acting factors in the GLUT1 gene that are targeted by this agonist remain elusive. Here we describe that the activity of the -99/+134 basal promoter of rat GLUT1 is increased by phenylephrine. Nevertheless, this is not mediated by previously described binding sites (GC-box, MG1E) in the promoter. Rather, the TATA box is required by the agonist to activate transcription from the promoter. Interestingly, The Ras-ERK mitogen-activated protein (MAP) kinase pathway is involved in the actions of phenylephrine on GLUT1 transcription, and the effects of Ras on the activity of the promoter depend on the integrity of the TATA box. Our data indicate that phenylephrine induces the expression of the TBP-associated factor TAF(II)250 mRNA, which increases in parallel to the expression of GLUT1, suggesting that altering the expression of basal transcription factors could be one mechanism by which phenylephrine may regulate the activity of the GLUT1 promoter.
Santalucía
Tomàs
T
National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Heart Science Centre, Harefield, Middlesex, UK. tsafat@iibb.csic.es
Sánchez-Feutrie
Manuela
M
Felkin
Leanne E
LE
Bhavsar
Pankaj K
PK
Barton
Paul J R
PJ
Zorzano
Antonio
A
Yacoub
Magdi H
MH
Brand
Nigel J
NJ
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051548:Histone Acetyltransferases; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D016385:TATA Box / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002316:Cardiotonic Agents; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D010656:Phenylephrine; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C089319:Ras-dependent mitogen-activated protein kinase kinase kinase