本文選題：激活素A + 激活素受體相互作用蛋白��； 參考：《吉林大學(xué)》2009年博士論文

【摘要】： 激活素A (Activin A),屬于轉(zhuǎn)化生長因子β(transforming-growth factor-β, TGF-β)超家族成員,又稱神經(jīng)細胞生存分子(nerve cell survival molecule)。 本研究在構(gòu)建激活素特異信號傳導(dǎo)蛋白——激活素受體相互作用蛋白1, 2(ARIP1, 2)基因表達載體及制備抗ARIP1, 2抗體的基礎(chǔ)上,采用Northern雜交、RT-PCR等分析了ARIP1, 2 mRNA在組織中的表達,發(fā)現(xiàn)ARIP1 mRNA在腦、垂體、睪丸、腎上腺組織表達;ARIP2 mRNA則在多種組織表達。免疫組織化學(xué)染色顯示,在大腦皮質(zhì)中,ARIP1主要表達在小細胞神經(jīng)元,而ARIP2主要表達在大細胞神經(jīng)元;在海馬和下丘腦神經(jīng)元、脈絡(luò)膜、垂體及小腦浦肯野細胞ARIP1和ARIP2共表達。小鼠腦神經(jīng)瘤細胞系Neuro-2a細胞也表達ARIP1和ARIP2,Activin A刺激Neuro-2a細胞24h后,ARIP1表達減弱,而ARIP2表達增強;LPS可促進ARIP1, 2表達。在Neuro-2a細胞ARIP1, 2過表達均能抑制Activin A誘導(dǎo)的特異基因轉(zhuǎn)錄,ARIP1還能抑制Smad3誘導(dǎo)的基因轉(zhuǎn)錄。Neuro-2a細胞穩(wěn)定轉(zhuǎn)染ARIP1基因表達質(zhì)粒可以顯著減弱Activin A誘導(dǎo)的INa,而ARIP2對Activin A誘導(dǎo)的INa無明顯影響。ARIP1基因過表達對Neuro-2a細胞增殖也有明顯的抑制作用,ARIP2基因過表達對增殖無明顯影響。在急性機械性腦損傷模型鼠腦組織中Activin A mRNA表達水平增高,而ARIP1表達減少,可能更有利于Activin A發(fā)揮神經(jīng)保護作用。 綜上所述,本研究結(jié)果顯示,作為激活素信號傳導(dǎo)的抑制蛋白,ARIP1, 2在組織中的表達及其生物學(xué)活性均存在差異,ARIP1, 2可能是決定Activin A在神經(jīng)細胞作用的關(guān)鍵信號傳導(dǎo)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R392

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