Ohba Norihiro, Maeda Mitsuyo, Nakagomi Saya, Muraoka Michinari, Kiyama Hiroshi
Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585 Japan.
Brain Res Mol Brain Res. 2003 Jul 23;115(2):147-56. doi: 10.1016/s0169-328x(03)00181-5.
It has been demonstrated that some of immediate early genes such as c-Jun are induced immediately and transiently following focal cerebral ischemia. Here we newly characterize the activating transcription factor (ATF)-3 as a focal ischemia associated immediate early gene. Using in situ hybridization and immunohistochemistry, we compared the expression profile of ATF-3 with those of ATF-2 and c-Jun after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced two temporal and spatial patterns of ATF-3 expression. Early and transient induction of ATF-3 mRNA was observed in the core and margins of the cortex immediately after MCA occlusion. Late-onset and prolonged expression of ATF-3 mRNA and its protein were specifically identified in the peri-infarct cortex and thalamus where neurons survive at least 1 month. The expression profiles of ATF-3 and c-Jun were virtually similar, but c-Jun expression was also observed in other regions of the brain in control rats. Expression of ATF-2 was ubiquitously seen in neuronal cells throughout the brain in normal rats, but was suppressed in ischemic regions. Double immunohistochemical labeling revealed concurrent expression of ATF-3 and phospho-c-Jun in neurons. We conclude that the transcription factor ATF-3 is a suitable marker of neurons subjected to ischemic insult directly and indirectly, and that cooperative works of ATF-3 and c-Jun may be crucial triggers of various transcriptional responses to the ischemic insult.
已经证实，一些即刻早期基因，如c-Jun，在局灶性脑缺血后会立即被短暂诱导。在此，我们新鉴定出活化转录因子（ATF）-3是一种与局灶性缺血相关的即刻早期基因。利用原位杂交和免疫组织化学技术，我们比较了大脑中动脉（MCA）闭塞后ATF-3与ATF-2和c-Jun的表达谱。局灶性脑缺血诱导了ATF-3表达的两种时空模式。MCA闭塞后立即在皮质的核心和边缘观察到ATF-3 mRNA的早期短暂诱导。在梗死周边皮质和丘脑（其中神经元至少存活1个月）中特异性鉴定出ATF-3 mRNA及其蛋白的迟发性和持续性表达。ATF-3和c-Jun的表达谱实际上相似，但在对照大鼠的大脑其他区域也观察到了c-Jun的表达。在正常大鼠中，ATF-2在全脑的神经元细胞中普遍表达，但在缺血区域受到抑制。双重免疫组织化学标记显示ATF-3和磷酸化c-Jun在神经元中共表达。我们得出结论，转录因子ATF-3是直接和间接遭受缺血损伤的神经元的合适标志物，并且ATF-3和c-Jun的协同作用可能是对缺血损伤的各种转录反应的关键触发因素。
