In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10)

Cellular Signalling
Angela McCahillMiles D Houslay

Abstract

Transcripts for the PDE4A10 cyclic AMP phosphodiesterase isoform are present in a wide variety of rat tissues including the heart. Sequence comparisons between the putative human and mouse promoters revealed a number of conserved regions including both an Sp1 and a CREB-binding site. The putative mouse PDE4A10 promoter was amplified from genomic DNA and sub-cloned into a luciferase reporter vector for investigation of activity in neonatal cardiac myocytes. Transfection with this construct identified a high level of luciferase expression in neonatal cardiac myocytes. Surprisingly, this activity was down-regulated by elevation of intracellular cAMP through a process involving PKA, but not EPAC, signalling. Such inhibition of the rodent PDE4A10 promoter activity in response to elevated cAMP levels is in contrast to the PDE4 promoters so far described. Site-directed mutagenesis revealed that the Sp1 binding site at promoter position -348 to -336 is responsible for the basal constitutive expression of murine PDE4A10. The conserved CREB-binding motif at position -370 to -363 also contributes to basal promoter activity but does not in itself confer cAMP inhibition upon the PDE4A10 promoter. EMSA analysis confirmed the authenticity of ...Continue Reading

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Citations

Dec 17, 2010·Basic Research in Cardiology·Wito RichterMarco Conti
Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lingzhi ZhangPaul A Insel
Mar 22, 2016·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·C Wu, S Rajagopalan
Apr 30, 2011·Physiological Reviews·Sharron H FrancisJackie D Corbin
Dec 2, 2011·Clinical Pharmacology and Therapeutics·J M MichalskiS I Rennard
Jul 26, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Issaka YougbareEric Rousseau

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