乙肝病毒X蛋白結(jié)合蛋白（hepatitis B X-interacting protein,HBXIP）可以調(diào)節(jié)乳腺癌中糖代謝重編程.為了研究HBXIP在生理?xiàng)l件下對(duì)糖代謝的調(diào)節(jié)作用及機(jī)制,本研究利用Cre/lox P重組酶系統(tǒng)成功構(gòu)建了肝臟組織中HBXIP特異敲除小鼠.當(dāng)小鼠接受刺激后,與正常組小鼠相比,肝臟HBXIP敲除小鼠表現(xiàn)基礎(chǔ)糖代謝功能異常,如葡萄糖、丙酮酸;相對(duì)于對(duì)照小鼠,肝臟HBXIP敲除小鼠對(duì)糖異生和胰島素耐受性減弱. RT-PCR、Western blot實(shí)驗(yàn)和免疫組化實(shí)驗(yàn)結(jié)果表明,HBXIP敲除小鼠肝臟組織中糖異生關(guān)鍵酶磷酸烯醇式丙酮酸羧化酶（phosphoenolpyruvate carboxykinase,PEPCK）表達(dá)顯著增加. QRT-PCR分析30例臨床肝組織中HBXIP m RNA和PEPCK m RNA表達(dá)水平發(fā)現(xiàn),HBXIP與PEPCK表達(dá)水平呈負(fù)相關(guān).熒光素酶報(bào)告基因?qū)嶒?yàn)和Ch IP實(shí)驗(yàn)結(jié)果表明HBXIP可以在基因轉(zhuǎn)錄水平調(diào)節(jié)PEPCK表達(dá).以上結(jié)果表明,HBXIP通過(guò)調(diào)節(jié)糖異生關(guān)鍵酶PEPCK的表達(dá)參與調(diào)控小鼠肝臟糖異生. 

【文章來(lái)源】：生物化學(xué)與生物物理進(jìn)展. 2019,46(02)北大核心SCICSCD

【文章頁(yè)數(shù)】：8 頁(yè)

【文章目錄】：
1 Introduction
2 Materials and methods
    2.1 Liver specific HBXIP knockout mice
    2.2 RT-PCR and qRT-PCR
    2.3 Histological analyses
    2.4 Cell culture
    2.5 Western blot analysis and small interference RNA (siRNA)
    2.6 Glucose tolerance test (GTT) and pyruate tolerance test (PTT)
    2.7 Luciferase reporter gene assays
    2.8 Chromatin immunoprecipitation (ChIP) assays
    2.9 Statistical analysis
3 Results
    3.1 Generation of liver-specific HBXIP-/-mice
    3.2 LiverHBXIP-/-mice display glucose metabolism dysregulation involving gluconeogenesis
    3.3 HBXIP is able to suppress PEPCK expression in liver
    3.4 HBXIP inhibits PEPCK at transcriptional level in liver
4 Discussion



本文編號(hào)：3185988