腦是富含膽固醇的器官,機體大約有25%的膽固醇集中在腦組織中.ATP結合盒超家族轉(zhuǎn)運蛋白對腦組織中膽固醇的膜外轉(zhuǎn)運和動態(tài)平衡起著重要的調(diào)節(jié)作用.研究發(fā)現(xiàn),ATP結合盒超家族轉(zhuǎn)運蛋白亞體ABCG1、ABCG4和ABCA1在成體腦組織中存在不同程度的表達,一種或多種亞體的缺失可以導致神經(jīng)退行性病變.然而,ATP結合盒超家族轉(zhuǎn)運蛋白亞體對腦發(fā)育過程中腦膽固醇動態(tài)變化的調(diào)節(jié)缺乏相關性的報道.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)育時期的腦組織,對ABCG1、ABCG4和ABCA1的mRNA與蛋白質(zhì)表達水平進行測定,并對腦組織和血清中ATP結合盒超家族轉(zhuǎn)運蛋白的表達水平與膽固醇水平的相關性進行研究.同時,使用ABCG1、ABCG4單一基因敲除鼠和ABCG1、ABCG4雙基因敲除鼠,研究ATP結合盒超家族轉(zhuǎn)運蛋白對與膽固醇合成的相關基因表達的影響以及對腦組織膽固醇代謝的調(diào)節(jié)作用.結果發(fā)現(xiàn),ABCG1、ABCG4和ABCA1在機體多個器官中均有表達,但ABCG1和ABCG4在小鼠腦組織中表達量最高.在腦組織發(fā)育過程中,ABCG1和ABCG4mRNA水平呈現(xiàn)明顯的表達時... 

【文章來源】：生物化學與生物物理進展. 2014,41(08)北大核心SCICSCD

【文章頁數(shù)】：12 頁

【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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