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(Circulation. 1995;92:2041-2043.)
© 1995 American Heart Association, Inc.

Articles

cAMP Response Element Binding Protein Is Expressed and Phosphorylated in the Human Heart

Frank Ulrich Müller, MD; Peter Bokník, PhD; Andreas Horst; Jörg Knapp, MD; Bettina Linck, MD; Wilhelm Schmitz, MD; Ute Vahlensieck, MD; Michael Böhm, MD; Mario C. Deng, MD; Hans H. Scheld, MD

From the Institut für Pharmakologie und Toxikologie (F.U.M., P.B., A.H., J.K., B.L., W.S., U.V.) and the Klinik und Poliklinik für Thorax-, Herz-, und Gefäßchirurgie (M.C.D., H.H.S.), Universität Münster (Germany) and the Medizinische Klinik III, Universität Köln (Germany).

Correspondence to Dr Frank Ulrich Müller, Institut für Pharmakologie und Toxikologie, Universität Münster, Domagkstraße 12, D-48129 Münster, Germany. E-mail mullerf@uni-muenster.de.

Background In end-stage failing human hearts and in rat hearts after prolonged in vivo ß-adrenergic treatment, several proteins involved in the cAMP-dependent signal transduction are altered on the protein, mRNA, or transcriptional level, eg, ß-adrenoceptors, G-proteins, or proteins of Ca²⁺ homeostasis. In many tissues, cAMP-dependent transcriptional 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 genes.

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 mobility shift assays. CRE specific binding was found in competition studies, and CREB and its phosphorylated form were immunologically identified in supershift experiments. The alternatively spliced CREB isoforms CREB327 and CREB341 were found to be expressed on the mRNA level by the reverse transcriptase–polymerase chain reaction.

Conclusions We conclude that in the failing and nonfailing human heart, CREB is expressed 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 human heart.

Key Words: cardiomyopathy • molecular biology • signal transduction

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