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(Circulation Research. 2003;93:6.)
© 2003 American Heart Association, Inc.

Editorials

ICER-Capades

Putting Cardiac Cyclic AMP Signaling "On Ice"

Mark A. Sussman

From the SDSU Heart Institute and Department of Biology, San Diego State University, San Diego, Calif.

Correspondence to Mark A. Sussman, SDSU Heart Institute and Department of Biology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182. E-mail sussman@sciences.sdsu.edu

Key Words: inducible cAMP early repressor • cyclic AMP • CRE signaling • hypertrophy • apoptosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Koyaanisquatsi: ko · yaa · nis · katsi [from the Hopi language], n. 1 crazy life. 2. life in turmoil. 3. life disintegrating. 4. life out of balance. 5. a state of life that calls for another way of living.

In the complex interconnected world of myocardial cell signaling, structure and function depend on balancing of positive and negative regulatory stimuli, sequentially or in tandem, to promote homeostatic conditions. Transient variations in balance of signal transduction are the norm as the myocardium dynamically adjusts to physiological demands and conditions. Fortunately, a finely tuned array of antagonistic signaling molecules normally keeps each other from running amok. However, when myocardial signaling suffers from koyaanisquatsi, the resultant cellular alterations lead to cardiomyopathic disease.

A healthy heart is highly responsive to catecholamines that stimulate adrenergic receptor signaling to increase contractile force.¹ ß-Adrenergic receptors transduce signals through G proteins that stimulate the classic G(s)-adenyl cyclase-3'-5'-adenosine monophosphate (cAMP) signaling cascade. The cAMP pathway senses and amplifies ß-adrenergic receptor activation, subsequently altering gene expression in conjunction with cAMP-response element binding (CREB) and cAMP-response element modulator (CREM) proteins.^2,3 cAMP-response elements (CREs) are found in the promoters of numerous genes regulating multiple facets of cell function.^2–4 CRE-mediated transactivation in cardiomyocytes undergoes a rapid "burst," peaking within 8 hours after induction followed by an attenuation phase characterized by a decrease in CRE-dependent transcription and refractoriness of transactivation by CREB, even in the presence of cAMP-elevating agonist.⁵ Several mechanisms have been explored to account for the attenuation phase . . . [Full Text of this Article]

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