Zuurbier C J, Smeele K M A, Eerbeek O
Laboratory of Experimental Intensive Care & Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Bioenerg Biomembr. 2009 Apr;41(2):181-5. doi: 10.1007/s10863-009-9209-7.
The interaction of hexokinase with mitochondria has emerged as a powerful mechanism in protecting many cell types against cell death. However, the role of mitochondrial hexokinase (mitoHK) in cardiac ischemia-reperfusion injury has as of yet received little attention. In this review we examine whether increased binding of hexokinase to the mitochondrion is also an integral component of cardioprotective signalling. We discuss observations in cardiac mitochondrial activation that directed us to the hypothesis of hexokinase cellular redistribution with reversible, cardioprotective ischemia, summarize the data showing that many cardioprotective interventions, such as ischemic preconditioning, insulin, morphine and volatile anesthetics, increase mitochondrial hexokinase binding within the intact heart, and discuss similarities between mitochondrial hexokinase association and ischemic preconditioning. Although most data indicate that mitochondrial hexokinase may indeed be an integral part of cardioprotection, a definitive proof for a causal relation between the amount of mitoHK and cardiac ischemia-reperfusion injury in the intact heart is eagerly awaited. When such relationship is indeed observed, the association of hexokinase with mitochondria will offer an opportunity to develop new therapies to combat ischemic cardiac diseases.
己糖激酶与线粒体的相互作用已成为保护多种细胞类型免于细胞死亡的一种强大机制。然而，线粒体己糖激酶（mitoHK）在心脏缺血再灌注损伤中的作用迄今很少受到关注。在本综述中，我们研究了己糖激酶与线粒体结合增加是否也是心脏保护信号传导的一个组成部分。我们讨论了在心脏线粒体激活中的观察结果，这些观察结果使我们提出了己糖激酶细胞重新分布与可逆性心脏保护缺血的假说，总结了表明许多心脏保护干预措施（如缺血预处理、胰岛素、吗啡和挥发性麻醉剂）会增加完整心脏中线粒体己糖激酶结合的数据，并讨论了线粒体己糖激酶结合与缺血预处理之间的相似性。尽管大多数数据表明线粒体己糖激酶可能确实是心脏保护的一个组成部分，但完整心脏中mitoHK的量与心脏缺血再灌注损伤之间因果关系的确切证据仍亟待证实。当确实观察到这种关系时，己糖激酶与线粒体的结合将为开发对抗缺血性心脏病的新疗法提供机会。
