腦是富含膽固醇的器官,機(jī)體大約有25%的膽固醇集中在腦組織中.ATP結(jié)合盒超家族轉(zhuǎn)運(yùn)蛋白對(duì)腦組織中膽固醇的膜外轉(zhuǎn)運(yùn)和動(dòng)態(tài)平衡起著重要的調(diào)節(jié)作用.研究發(fā)現(xiàn),ATP結(jié)合盒超家族轉(zhuǎn)運(yùn)蛋白亞體ABCG1、ABCG4和ABCA1在成體腦組織中存在不同程度的表達(dá),一種或多種亞體的缺失可以導(dǎo)致神經(jīng)退行性病變.然而,ATP結(jié)合盒超家族轉(zhuǎn)運(yùn)蛋白亞體對(duì)腦發(fā)育過(guò)程中腦膽固醇動(dòng)態(tài)變化的調(diào)節(jié)缺乏相關(guān)性的報(bào)道.在本研究中,從低膽固醇飲食喂養(yǎng)的C57BL/6J小鼠中獲取出生后不同發(fā)育時(shí)期的腦組織,對(duì)ABCG1、ABCG4和ABCA1的mRNA與蛋白質(zhì)表達(dá)水平進(jìn)行測(cè)定,并對(duì)腦組織和血清中ATP結(jié)合盒超家族轉(zhuǎn)運(yùn)蛋白的表達(dá)水平與膽固醇水平的相關(guān)性進(jìn)行研究.同時(shí),使用ABCG1、ABCG4單一基因敲除鼠和ABCG1、ABCG4雙基因敲除鼠,研究ATP結(jié)合盒超家族轉(zhuǎn)運(yùn)蛋白對(duì)與膽固醇合成的相關(guān)基因表達(dá)的影響以及對(duì)腦組織膽固醇代謝的調(diào)節(jié)作用.結(jié)果發(fā)現(xiàn),ABCG1、ABCG4和ABCA1在機(jī)體多個(gè)器官中均有表達(dá),但ABCG1和ABCG4在小鼠腦組織中表達(dá)量最高.在腦組織發(fā)育過(guò)程中,ABCG1和ABCG4mRNA水平呈現(xiàn)明顯的表達(dá)時(shí)... 

【文章來(lái)源】：生物化學(xué)與生物物理進(jìn)展. 2014,41(08)北大核心SCICSCD

【文章頁(yè)數(shù)】：12 頁(yè)

【文章目錄】：
1 Materials and methods
    1.1 Reagents
    1.2 Mice
    1.3 Real-time quantitative PCR analysis of ABCG1, ABCG4 and ABCA1 m RNA expression
    1.4 Immunoblots analysis of ABCG1, ABCG4and ABCA1 protein expression
    1.5 Freecholesterol (FC) and
    1.6 Analysis of data and statistical analysis
2 Results
    2.1 ABCG1 and ABCG4, but not ABCA1, mainly expressed in adult brain
    2.2 ABCG1 and ABCG4 m RNA levels peaked at 4 2 days of age, while ABCA1 m RNA levels were near baseline
    2.3 ABCG1 protein levels peaked at day 28 then decreased, while ABCG4 levels peaked at day 42, and ABCA1 levels remained near baseline
    2.4 Circulating plasma and brain esterifiedcholesterol levels exhibited a biphasic distribution, which peaked at day 42
    2.5 ABCG1 and ABCG4 expressed reciprocally in Abcg1 or Abcg4 knockout mice (Abcg1-/-orAbcg4-/-)
    2.6 Brain free and esterified cholesterol levels increased in ABCG1-/-ABCG4-/-mice
    2.7 Changes of genes expression in ABCG1-/-ABCG4-/-mice brains
3 Discussion



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