Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida 33101, USA.
Antioxid Redox Signal. 2011 May 15;14(10):1853-61. doi: 10.1089/ars.2010.3467. Epub 2011 Jan 5.
Cerebral ischemia is defined as little or no blood flow in cerebral circulation, characterized by low tissue oxygen and glucose levels, which promotes neuronal mitochondria dysfunction leading to cell death. A strategy to counteract cerebral ischemia-induced neuronal cell death is ischemic preconditioning (IPC). IPC results in neuroprotection, which is conferred by a mild ischemic challenge prior to a normally lethal ischemic insult. Although many IPC-induced mechanisms have been described, many cellular and subcellular mechanisms remain undefined. Some reports have suggested key signal transduction pathways of IPC, such as activation of protein kinase C epsilon, mitogen-activated protein kinase, and hypoxia-inducible factors, that are likely involved in IPC-induced mitochondria mediated-neuroprotection. Moreover, recent findings suggest that signal transducers and activators of transcription (STATs), a family of transcription factors involved in many cellular activities, may be intimately involved in IPC-induced ischemic tolerance. In this review, we explore current signal transduction pathways involved in IPC-induced mitochondria mediated-neuroprotection, STAT activation in the mitochondria as it relates to IPC, and functional significance of STATs in cerebral ischemia.
脑缺血定义为大脑循环中血液流量减少或停止，其特征是组织中的氧和葡萄糖水平降低，这会促进神经元线粒体功能障碍，导致细胞死亡。对抗脑缺血引起的神经元细胞死亡的一种策略是缺血预处理（IPC）。IPC 会导致神经保护，这是由正常致死性缺血损伤之前的轻度缺血挑战引起的。尽管已经描述了许多 IPC 诱导的机制，但许多细胞和亚细胞机制仍未定义。一些报告表明，IPC 诱导的关键信号转导途径，如蛋白激酶 C epsilon、丝裂原活化蛋白激酶和缺氧诱导因子的激活，可能参与了 IPC 诱导的线粒体介导的神经保护。此外，最近的研究结果表明，信号转导子和转录激活子（STATs），一种参与许多细胞活动的转录因子家族，可能与 IPC 诱导的缺血耐受密切相关。在这篇综述中，我们探讨了与 IPC 诱导的线粒体介导的神经保护相关的当前信号转导途径、与 IPC 相关的线粒体中 STAT 的激活以及 STATs 在脑缺血中的功能意义。
