Simkhovich Boris Z, Przyklenk Karin, Kloner Robert A
1Heart Institute, Good Samaritan Hospital, Los Angeles, CA, USA.
J Cardiovasc Pharmacol Ther. 2013 Nov;18(6):525-32. doi: 10.1177/1074248413494814. Epub 2013 Jul 19.
Since the discovery of ischemic preconditioning (IPC) 26 years ago, numerous studies attempted to determine the mechanism of this powerful form of cardioprotection. One of the first proposed pathways of IPC suggested that the preconditioning stimulus activated phospholipase C via G-protein, and diacylglycerol released from phospholipid moieties activated protein kinase C (PKC) by translocating it from the cytosol to the sarcolemmal membranes. The major protective isoform of PKC was found to be the PKC-∈. Despite some contradictions and controversies, today even the most skeptical opponents acknowledge that PKC plays a significant role in the mechanism of IPC. During recent years, both the role and the place of PKC-∈ in the mechanism of IPC have been revised. The current review presents the evolution of the "PKC theory" and summarizes the most recent data regarding the role of PKC in IPC. In addition to classical IPC, PKC appears to play a role in the mechanisms of newer conditioning protocols, that is, remote IPC and ischemic postconditioning.
自26年前发现缺血预处理(IPC)以来,众多研究试图确定这种强大的心脏保护形式的机制。最早提出的IPC途径之一表明,预处理刺激通过G蛋白激活磷脂酶C,从磷脂部分释放的二酰基甘油通过将蛋白激酶C(PKC)从胞质溶胶转运到肌膜而激活它。PKC的主要保护性亚型被发现是PKC-∈。尽管存在一些矛盾和争议,但如今即使是最持怀疑态度的反对者也承认PKC在IPC机制中发挥着重要作用。近年来,PKC-∈在IPC机制中的作用和地位都已得到修正。本综述介绍了“PKC理论”的演变,并总结了关于PKC在IPC中作用的最新数据。除了经典的IPC外,PKC似乎在更新的预处理方案即远程IPC和缺血后处理的机制中也发挥作用。