doi: 10.1161/CIRCULATIONAHA.107.713115
(Circulation. 2008;117:832-840.)
© 2008 American Heart Association, Inc.
Basic Science for Clinicians |
AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra
From the Departments of Internal Medicine (Section of Cardiovascular Medicine) and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Conn.
Correspondence to Lawrence H. Young, MD, 333 Cedar St, New Haven, CT 06520. E-mail lawrence.young@yale.edu
Key Words: AMP kinase • fatty acids • glucose • ischemia • signal transduction
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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The heart is subjected to physiological stress in normal individuals during exercise and to pathological stress in patients with ischemic disease, ventricular pressure, or volume overload. How the heart responds depends on the type, intensity, and duration of the stress. Just as extrinsic physiological reflexes are activated when cardiac output falls, internal molecular sensors respond to changes in physiological parameters within cardiac cells. These specialized molecules sense perturbations in oxygen tension, cell stretch, pH, membrane potential, oxidative state, and intracellular energy stores, with the latter particularly pertinent to this discussion.
The present article will focus on the AMP-activated protein kinase (AMPK), a molecular stress response pathway that is activated by increases in the intracellular concentration of AMP. AMP is not to be confused with cAMP, a molecular signal produced during stress by catecholamine-induced β-adrenergic stimulation. The AMPK pathway has received a great deal of attention because of its potential importance in the ischemic heart,1,2 diabetes,3 and cancer.4 Several recent reviews have summarized scientific discoveries related to AMPK and can provide the interested reader with additional insights into the field.2,5–7 The present article will strive to provide a perspective that is accessible to the clinician with an interest in contemporary basic science research. It is hoped that the reader will develop an understanding of how AMPK functions in the heart to orchestrate the cellular response to ischemic stress.
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AMP and Cellular Energy Stress |
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Cells have evolved elaborate mechanisms to protect themselves against changes in their environment. In the heart, one of the most important forms of
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