Zarrinpashneh Elham, Carjaval Karla, Beauloye Christophe, Ginion Audrey, Mateo Philippe, Pouleur Anne-Catherine, Horman Sandrine, Vaulont Sophie, Hoerter Jacqueline, Viollet Benoit, Hue Louis, Vanoverschelde Jean-Louis, Bertrand Luc
Division of Cardiology, Université catholique de Louvain, B-1200 Brussels, Belgium.
Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2875-83. doi: 10.1152/ajpheart.01032.2005. Epub 2006 Jul 28.
AMP-activated protein kinase (AMPK) is a major sensor and regulator of the energetic state of the cell. Little is known about the specific role of AMPKalpha(2), the major AMPK isoform in the heart, in response to global ischemia. We used AMPKalpha(2)-knockout (AMPKalpha(2)(-/-)) mice to evaluate the consequences of AMPKalpha(2) deletion during normoxia and ischemia, with glucose as the sole substrate. Hemodynamic measurements from echocardiography of hearts from AMPKalpha(2)(-/-) mice during normoxia showed no significant modification compared with wild-type animals. In contrast, the response of hearts from AMPKalpha(2)(-/-) mice to no-flow ischemia was characterized by a more rapid onset of ischemia-induced contracture. This ischemic contracture was associated with a decrease in ATP content, lactate production, glycogen content, and AMPKbeta(2) content. Hearts from AMPKalpha(2)(-/-) mice were also characterized by a decreased phosphorylation state of acetyl-CoA carboxylase during normoxia and ischemia. Despite an apparent worse metabolic adaptation during ischemia, the absence of AMPKalpha(2) does not exacerbate impairment of the recovery of postischemic contractile function. In conclusion, AMPKalpha(2) is required for the metabolic response of the heart to no-flow ischemia. The remaining AMPKalpha(1) cannot compensate for the absence of AMPKalpha(2).
AMP激活的蛋白激酶（AMPK）是细胞能量状态的主要传感器和调节器。关于心脏中主要的AMPK亚型AMPKα(2)在全局缺血反应中的具体作用，人们了解甚少。我们使用AMPKα(2)基因敲除（AMPKα(2)(-/-)）小鼠，以葡萄糖作为唯一底物，评估在常氧和缺血期间AMPKα(2)缺失的后果。与野生型动物相比，在常氧期间对AMPKα(2)(-/-)小鼠心脏进行超声心动图血流动力学测量未显示出显著改变。相反，AMPKα(2)(-/-)小鼠心脏对无血流缺血的反应表现为缺血诱导的挛缩发作更快。这种缺血性挛缩与ATP含量、乳酸生成、糖原含量和AMPKβ(2)含量的降低有关。AMPKα(2)(-/-)小鼠的心脏在常氧和缺血期间还表现为乙酰辅酶A羧化酶的磷酸化状态降低。尽管在缺血期间明显存在较差的代谢适应性，但AMPKα(2)的缺失并不会加剧缺血后收缩功能恢复的损伤。总之，AMPKα(2)是心脏对无血流缺血代谢反应所必需的。剩余的AMPKα(1)无法弥补AMPKα(2)的缺失。
