Kuramoto N, Azuma Y, Inoue K, Ogita K, Mitani A, Zhang L, Yanase H, Masuda S, Kataoka K, Yoneda Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan.
Brain Res. 1998 Sep 28;806(2):152-64. doi: 10.1016/s0006-8993(98)00693-3.
Protein biosynthesis is mainly under the control at the level of gene transcription in eukaryotes. Transcription factors are nuclear proteins with abilities to modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNA from double stranded DNA in the cell nuclei. Binding of a radiolabeled oligonucleotide probe for the transcription factor activator protein-1 (AP1) was transiently potentiated 1 to 6 h after the recirculation of blood supply in the thalamus and striatum, but not in the entorhinal cortex, olfactory bulb, frontal cortex, cerebellar cortex and medulla-pons, in gerbils with transient global forebrain ischemia for 5 min, in addition to the hippocampal subregions. The ischemic insult not only increased the immunoreactivity with an antibody against cyclic AMP response element binding protein (CREB) phosphorylated at serine133, but also induced the expression of both c-Jun and c-Fos family proteins 3 h after the recirculation in the thalamus. Limited proteolysis by Staphylococcus aureus (S. aureus) V8 protease revealed the expression of different partner proteins of AP1 in response to ischemic signals in the thalamus. Moreover, ischemia for 2 min led to more prolonged elevation of AP1 binding in the thalamus at least up to 12 h after the reperfusion than that seen with ischemia for 5 min. These results suggest that potentiation of AP1 DNA binding may at least in part involve mechanisms associated with the expression of c-Fos protein through phosphorylation of CREB at serine133 in the thalamus of gerbils with ischemia.
在真核生物中，蛋白质生物合成主要在基因转录水平受到调控。转录因子是核蛋白，具有调节RNA聚合酶II活性的能力，RNA聚合酶II负责在细胞核中由双链DNA形成信使RNA。在短暂全脑缺血5分钟的沙鼠中，除海马亚区外，丘脑和纹状体供血再循环后1至6小时，转录因子激活蛋白-1（AP1）的放射性标记寡核苷酸探针结合瞬时增强，但在内嗅皮质、嗅球、额叶皮质、小脑皮质和延髓-脑桥中未出现这种情况。缺血损伤不仅增加了与抗丝氨酸133磷酸化的环磷酸腺苷反应元件结合蛋白（CREB）抗体的免疫反应性，还在丘脑再循环3小时后诱导了c-Jun和c-Fos家族蛋白的表达。金黄色葡萄球菌（S. aureus）V8蛋白酶的有限蛋白水解揭示了丘脑中AP1不同伴侣蛋白对缺血信号的表达响应。此外，与5分钟缺血相比，2分钟缺血导致丘脑AP1结合在再灌注后至少12小时内的升高持续时间更长。这些结果表明，AP1 DNA结合的增强可能至少部分涉及与沙鼠丘脑缺血时通过丝氨酸133磷酸化CREB来表达c-Fos蛋白相关的机制。
