CAMP RESPONSE ELEMENT-BINDING PROTEIN IS EXPRESSED AND PHOSPHORYLATEDIN THE HUMAN HEART

Background In end-stage failing human hearts and in rat hearts after p rolonged in vivo beta-adrenergic treatment, several proteins involved in the cAMP-dependent signal transduction are altered on the protein, mRNA, or transcriptional level, eg, alpha-adrenoceptors, G-proteins, o r proteins of Ca2+ homeostasis. In many tissues, cAMP-dependent transc riptional regulation occurs through the cAMP response element binding protein (CREB) and related transcription factors binding as dimers to cAMP response elements (CREs) in the promoter regions of regulated gen es. Methods and Results To investigate a possible role of CREB in the human heart, nuclear protein of explanted failing and nonfailing human hearts was used to test for CRE specific binding properties in gel mo bility shift assays. CRE specific binding was found in competition stu dies. and CREB and its phosphorylated form were immunologically identi fied in supershift experiments. The alternatively spliced CREB isoform s CREB327 and CREB341 were found to be expressed on the mRNA level by the reverse transcriptase-polymerase chain reaction. Conclusions We co nclude that in the failing and nonfailing human heart, CREB is express ed on the protein and mRNA levels and that CREB is phosphorylated and able to bind to CREs, indicating a functional role of CREB in the huma n heart.