Danan Ilan J, Rashed Eman R, Depre Christophe
Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Cardiovasc Drug Rev. 2007 Spring;25(1):14-29. doi: 10.1111/j.1527-3466.2007.00002.x.
H11 kinase (H11K) is a small heat shock protein expressed predominantly in the heart and skeletal muscle, which plays a critical role in the maintenance of cardiac cell survival and in promoting cell growth through the activation of complementary signaling pathways. An overexpression of H11K was detected in various forms of heart disease, both in animal models and in patients, including acute and chronic ventricular dysfunction, and myocardial hypertrophy. Overexpression of H11K was reproduced in a cardiac-specific transgenic model, which led to significant progress in understanding the role and mechanism of action of the protein. Increased expression of H11K confers a cardioprotection that is equivalent to ischemic preconditioning; it promotes cardiac hypertrophy while maintaining contractile function. The overexpression of H11K is sufficient to activate most of the signaling pathways involved in cardiac cell growth and survival, including the phosphatidylinositol-3-kinase/Akt pathway, the AMP-dependent protein kinase, the PKCepsilon pathway of ischemic preconditioning, the nitric oxide pathway of delayed cardioprotection, and the mTOR pathway of cell growth. As a result, the survival response triggered by H11K in the heart includes antiapoptosis, cytoprotection, preconditioning, growth, and metabolic stimulation. In addition to activating signaling pathways, H11K promotes the subcellular translocation and crosstalk of intracellular messengers. This review discusses the biological function of H11K, its molecular mechanisms of action, and its potential therapeutic relevance. In particular, we discuss how preemptive conditioning of the heart by H11K might be beneficial for patients with ischemic heart disease who would be at risk of further irreversible cardiac damage.
H11激酶（H11K）是一种主要在心脏和骨骼肌中表达的小分子热休克蛋白，它在维持心脏细胞存活以及通过激活互补信号通路促进细胞生长方面发挥着关键作用。在动物模型和患者的各种心脏病中均检测到H11K的过表达，包括急性和慢性心室功能障碍以及心肌肥大。在心脏特异性转基因模型中重现了H11K的过表达，这在理解该蛋白的作用和作用机制方面取得了重大进展。H11K表达增加赋予了相当于缺血预处理的心脏保护作用；它促进心脏肥大，同时维持收缩功能。H11K的过表达足以激活参与心脏细胞生长和存活的大多数信号通路，包括磷脂酰肌醇-3-激酶/Akt通路、AMP依赖性蛋白激酶、缺血预处理的PKCε通路、延迟心脏保护的一氧化氮通路以及细胞生长的mTOR通路。因此，H11K在心脏中触发的存活反应包括抗凋亡、细胞保护、预处理、生长和代谢刺激。除了激活信号通路外，H11K还促进细胞内信使的亚细胞转位和相互作用。本综述讨论了H11K的生物学功能、其分子作用机制及其潜在的治疗意义。特别是，我们讨论了H11K对心脏的预先调节如何可能对有进一步不可逆心脏损伤风险的缺血性心脏病患者有益。
