激活素受体相互作用蛋白1，2在小鼠脑组织中的表达及分布的比较研究

发布时间：2018-04-28 10:42

本文选题：激活素A + 激活素受体相互作用蛋白　；参考：《吉林大学》2009年博士论文

【摘要】： 激活素A (Activin A),属于转化生长因子β(transforming-growth factor-β, TGF-β)超家族成员,又称神经细胞生存分子(nerve cell survival molecule)。本研究在构建激活素特异信号传导蛋白——激活素受体相互作用蛋白1, 2(ARIP1, 2)基因表达载体及制备抗ARIP1, 2抗体的基础上,采用Northern杂交、RT-PCR等分析了ARIP1, 2 mRNA在组织中的表达,发现ARIP1 mRNA在脑、垂体、睾丸、肾上腺组织表达;ARIP2 mRNA则在多种组织表达。免疫组织化学染色显示,在大脑皮质中,ARIP1主要表达在小细胞神经元,而ARIP2主要表达在大细胞神经元;在海马和下丘脑神经元、脉络膜、垂体及小脑浦肯野细胞ARIP1和ARIP2共表达。小鼠脑神经瘤细胞系Neuro-2a细胞也表达ARIP1和ARIP2,Activin A刺激Neuro-2a细胞24h后,ARIP1表达减弱,而ARIP2表达增强;LPS可促进ARIP1, 2表达。在Neuro-2a细胞ARIP1, 2过表达均能抑制Activin A诱导的特异基因转录,ARIP1还能抑制Smad3诱导的基因转录。Neuro-2a细胞稳定转染ARIP1基因表达质粒可以显著减弱Activin A诱导的INa,而ARIP2对Activin A诱导的INa无明显影响。ARIP1基因过表达对Neuro-2a细胞增殖也有明显的抑制作用,ARIP2基因过表达对增殖无明显影响。在急性机械性脑损伤模型鼠脑组织中Activin A mRNA表达水平增高,而ARIP1表达减少,可能更有利于Activin A发挥神经保护作用。综上所述,本研究结果显示,作为激活素信号传导的抑制蛋白,ARIP1, 2在组织中的表达及其生物学活性均存在差异,ARIP1, 2可能是决定Activin A在神经细胞作用的关键信号传导分子。
[Abstract]:Activin A, a member of transforming growth factor 尾 transforming-growth factor- 尾 (TGF- 尾) superfamily, is also known as nerve cell survival molecule. In this study, the expression vector of activin-specific signal transduction protein-activin receptor interaction protein (ARIP1,2) was constructed and the anti-ARIP1,2 antibody was prepared. The expression of ARIP1,2 mRNA in tissues was analyzed by Northern hybridization and RT-PCR. It was found that ARIP1 mRNA was expressed in brain, pituitary, testis and adrenal gland, and ARIP2 mRNA was expressed in various tissues. Immunohistochemical staining showed that AARIP1 was mainly expressed in small cell neurons, while ARIP2 was mainly expressed in large cell neurons in cerebral cortex, and ARIP1 and ARIP2 in hippocampal and hypothalamic neurons, choroid, pituitary and Purkinje cells in cerebellum. Mouse brain neuroma cell line Neuro-2a also expressed ARIP1 and ARIP2Activin A stimulated Neuro-2a cells for 24 hours, and the expression of ARIP1 was decreased after stimulation of Neuro-2a cells with ARIP2. Overexpression of ARIP1 and 2 in Neuro-2a cells could inhibit the specific gene transcription induced by Activin A. ARIP1 could also inhibit Smad3 induced gene transcription. Neuro-2a cells transfected ARIP1 gene expression plasmid stably could significantly weaken INA induced by Activin A, while ARIP2 induced Activin A. The overexpression of ARIP1 gene also inhibited the proliferation of Neuro-2a cells. The overexpression of ARIP2 gene did not affect the proliferation of Neuro-2a cells. The increase of Activin A mRNA expression and the decrease of ARIP1 expression in the brain tissue of acute mechanical brain injury model may be more beneficial to the neuroprotective effect of Activin A. In conclusion, our results suggest that the expression and biological activity of ARIP1, 2, an inhibitor of activin signal transduction, are different in tissues. ARIP1, 2 may be the key signal transduction molecules that determine the action of Activin A in nerve cells.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R392

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