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小鼠脑中的NF-κB样因子。发育调控及组织特异性表达。

NF-kappa B-like factors in the murine brain. Developmentally-regulated and tissue-specific expression.

作者信息

Yakovleva T, Terenius L

机构信息

Department of Drug Dependence Research, Karolinska Institute, Stockholm, Sweden.

出版信息

Brain Res Mol Brain Res. 1993 Oct;20(1-2):137-46. doi: 10.1016/0169-328x(93)90119-a.

DOI:10.1016/0169-328x(93)90119-a
PMID:8255175
Abstract

NF-kappa B and related factors are important transducers of external signals to the cell nucleus. They are abundant in the brain, where they may be significant for the regulation of gene transcription in plasticity-related processes for instance, via activation of protein kinase C. The subunit composition and levels of these factors in the mouse and rat brain and other tissues, using an assay based on gel retardation of the oligonucleotides corresponding to the kappa B DNA-element, are reported here. Three major kappa B-binding factors were observed. Factors I and II were activated by the dissociating agent deoxycholate. DNA protein cross-linking and antibody neutralization experiments suggest that factor I is a heterodimer of c-Rel and p65; factor II is a heterodimer of p50 and p65 (authentic NF-kappa B), and of p50 and c-Rel; factor III is the p50 homodimer (KBF1). All three factors were generally expressed in the 17-day-old rat embryo and 5-day-old pup, whereas in the adult rat, expression was more limited and showed certain tissue specificity. Factor II was the most generally expressed and the only factor observed in adult brain. Factor I was only detected in the adult testis whereas factor III was observed in the adult spleen and, in small amounts, in the liver and lung. Two minor kappa B-specific factors (A and B), distinctive to the brain and spleen, respectively, showed very slow gel mobility. Their estimated molecular weights were about 125 kDa and 95 kDa, respectively. Expression of factor A was stable in the rat brain during development. Factor A may be identical to a previously described brain-specific factor, BETA (Korner et al., Neuron, 3 (1989) 563-572). Thus, the expression pattern of kappa B-binding activities is apparently developmentally regulated and tissue-specific particularly in the adult. In the adult mouse and rat brain, only factors II (probably NF-kappa B and p50/c-Rel heterodimer) and A (probably BETA) could be observed.

摘要

核因子-κB及相关因子是外部信号向细胞核传导的重要转导分子。它们在大脑中含量丰富,在可塑性相关过程中对基因转录的调节可能具有重要意义,例如通过激活蛋白激酶C发挥作用。本文报道了利用基于与κB DNA元件相对应的寡核苷酸凝胶阻滞分析,检测小鼠和大鼠大脑及其他组织中这些因子的亚基组成和水平。观察到三种主要的κB结合因子。因子I和因子II可被解离剂脱氧胆酸盐激活。DNA-蛋白质交联和抗体中和实验表明,因子I是c-Rel和p65的异二聚体;因子II是p50和p65(真正的核因子-κB)以及p50和c-Rel的异二聚体;因子III是p50同二聚体(KBF1)。这三种因子在17日龄大鼠胚胎和5日龄幼崽中普遍表达,而在成年大鼠中,表达则较为局限且具有一定的组织特异性。因子II是表达最普遍的,也是在成年大脑中观察到的唯一因子。因子I仅在成年睾丸中检测到,而因子III在成年脾脏中观察到,在肝脏和肺中少量存在。两种分别在大脑和脾脏中特异的次要κB特异性因子(A和B),其凝胶迁移率非常缓慢。它们的估计分子量分别约为125 kDa和95 kDa。因子A在大鼠大脑发育过程中的表达稳定。因子A可能与先前描述的大脑特异性因子BETA相同(科尔纳等人,《神经元》,3(1989年)563 - 572)。因此,κB结合活性的表达模式显然受到发育调控且具有组织特异性,在成年期尤为明显。在成年小鼠和大鼠大脑中,仅能观察到因子II(可能是核因子-κB和p50/c-Rel异二聚体)和因子A(可能是BETA)。

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