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(xì)胞生存分子(nerve cell survival molecule)。 本研究在構(gòu)建激活素特異信號(hào)傳導(dǎo)蛋白——激活素受體相互作用蛋白1, 2(ARIP1, 2)基因表達(dá)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(dá),發(fā)現(xiàn)ARIP1 mRNA在腦、垂體、睪丸、腎上腺組織表達(dá);ARIP2 mRNA則在多種組織表達(dá)。免疫組織化學(xué)染色顯示,在大腦皮質(zhì)中,ARIP1主要表達(dá)在小細(xì)胞神經(jīng)元,而ARIP2主要表達(dá)在大細(xì)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(xì)胞ARIP1和ARIP2共表達(dá)。小鼠腦神經(jīng)瘤細(xì)胞系Neuro-2a細(xì)胞也表達(dá)ARIP1和ARIP2,Activin A刺激Neuro-2a細(xì)胞24h后,ARIP1表達(dá)減弱,而ARIP2表達(dá)增強(qiáng);LPS可促進(jìn)ARIP1, 2表達(dá)。在Neuro-2a細(xì)胞ARIP1, 2過表達(dá)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(xì)胞穩(wěn)定轉(zhuǎn)染ARIP1基因表達(dá)質(zhì)�？梢燥@著減弱Activin A誘導(dǎo)的INa,而ARIP2對(duì)Activin A誘導(dǎo)的INa無明顯影響。ARIP1基因過表達(dá)對(duì)Neuro-2a細(xì)胞增殖也有明顯的抑制作用,ARIP2基因過表達(dá)對(duì)增殖無明顯影響。在急性機(jī)械性腦損傷模型鼠腦組織中Activin A mRNA表達(dá)水平增高,而ARIP1表達(dá)減少,可能更有利于Activin A發(fā)揮神經(jīng)保護(hù)作用。 綜上所述,本研究結(jié)果顯示,作為激活素信號(hào)傳導(dǎo)的抑制蛋白,ARIP1, 2在組織中的表達(dá)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(xì)胞作用的關(guān)鍵信號(hào)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(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 方琳;柳忠輝;劉永茂;臺(tái)桂香;;激活素促進(jìn)雞胚神經(jīng)節(jié)神經(jīng)突起生長作用[J];動(dòng)物學(xué)雜志;2006年06期

2 華仲慰;神經(jīng)系統(tǒng)可塑性研究的進(jìn)展[J];生理科學(xué)進(jìn)展;1986年01期

3 方琳;劉永茂;葛敬巖;劉海巖;臺(tái)桂香;柳忠輝;;激活素結(jié)合蛋白阻斷激活素誘導(dǎo)雞胚神經(jīng)節(jié)神經(jīng)突起生長作用及其機(jī)制研究[J];中風(fēng)與神經(jīng)疾病雜志;2007年04期

4 石祥恩,趙雅度;顱腦損傷治療研究的一些進(jìn)展[J];中華創(chuàng)傷雜志;1996年02期

5 易聲禹;重型顱腦損傷救治幾個(gè)關(guān)鍵問題的處理[J];中華神經(jīng)外科雜志;1999年01期

6 ;Cloning of the full-length gene of activin receptor-interacting protein2a and characterization of its interaction with ActR Ⅱ A[J];Progress in Natural Science;2007年02期

，

本文編號(hào)：1814928