Song Juhyun, Cheon So Yeong, Lee Won Taek, Park Kyung Ah, Lee Jong Eun
Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea; BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Brain Res. 2015 Jan 21;1595:143-55. doi: 10.1016/j.brainres.2014.11.024. Epub 2014 Nov 15.
Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia.
凋亡信号调节激酶1（ASK1）是丝裂原活化蛋白激酶激酶激酶（MAPKKK），参与各种中枢神经系统（CNS）信号通路。在脑缺血中，脑内血管通透性是一个重要问题，因为其调节失败会导致水肿形成和血脑屏障（BBB）破坏。为了确定ASK1在脑缺血后血管通透性和水肿形成中的作用，我们首先使用缺血脑组织的微阵列分析来研究ASK1相关基因表达。然后我们测量了缺氧损伤后脑内皮细胞中ASK1和血管内皮生长因子（VEGF）的蛋白水平。我们还使用ASK1小干扰RNA（ASK1-siRNA）通过对缺血脑组织进行甲酚紫染色来检测ASK1和VEGF的蛋白表达、水肿形成及形态学改变。最后，进行免疫组织化学检查缺血性脑损伤中VEGF和水通道蛋白-1（AQP-1）的表达。基于我们的研究结果，我们提出ASK1是脑缺血中血管通透性和水肿形成的调节因子。
