Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
J Mol Cell Cardiol. 2011 Oct;51(4):548-53. doi: 10.1016/j.yjmcc.2010.12.004. Epub 2010 Dec 13.
AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis and multiple biological processes in cell growth and survival, hence an attractive drug target. AMPK is a heterotrimeric protein consisting of α catalytic, β and γ regulatory subunits; two isoforms of each subunit are present in the heart. Studies using both genetic and pharmacological approaches have demonstrated important roles of AMPK in protecting the heart during ischemia/reperfusion injury as well as in pathological hypertrophy and failure. There is also emerging evidence suggesting isoform-specific function of AMPK, e.g. mutations of the γ2 subunit cause human cardiomyopathy. Thus, strategies avoiding the undesirable effects of altering γ2-AMPK activity, such as isoform selective activation of AMPK may lead to cardioprotective therapies with greater efficacy and safety. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."
腺苷酸活化蛋白激酶 (AMPK) 调节细胞能量稳态和细胞生长与存活中的多种生物学过程，因此是一个有吸引力的药物靶点。AMPK 是一种由α催化亚基、β和γ调节亚基组成的异三聚体蛋白；每个亚基都有两种同工型存在于心脏中。使用遗传和药理学方法的研究表明，AMPK 在缺血/再灌注损伤以及病理性肥大和衰竭期间保护心脏方面发挥着重要作用。也有新的证据表明 AMPK 的同工型特异性功能，例如 γ2 亚基的突变导致人类心肌病。因此，避免改变 γ2-AMPK 活性的不良影响的策略，例如 AMPK 的同工型选择性激活，可能会导致更有效和更安全的心脏保护治疗。本文是题为“肥大和心力衰竭中的关键信号分子”的特刊的一部分。
