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  本文關(guān)鍵詞：四氫生物蝶呤對小鼠成纖維細(xì)胞糖代謝的作用機制　出處：《華僑大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 四氫生物蝶呤 葡萄糖 糖酵解 成纖維細(xì)胞

【摘要】：與正常分化的細(xì)胞不同，多數(shù)增殖細(xì)胞和腫瘤細(xì)胞通過有氧糖酵解的方式為細(xì)胞生理過程提供能量，即“Warburg效應(yīng)”。這種快速有效的代謝重編程滿足了增殖細(xì)胞對生物大分子合成和能量需求。此外，乳酸的大量排出改變了細(xì)胞外的微環(huán)境，為腫瘤細(xì)胞的存活、生長和侵襲創(chuàng)造了有利條件。 四氫生物蝶呤（BH4）是芳香族氨基酸羥化酶和一氧化氮合酶的輔因子。BH4有兩種合成途徑：從頭合成和補救合成。其中GTPCH是從頭合成中的限速酶，墨蝶呤是補救合成中的底物�；蛐酒Y(jié)果顯示，，GCH基因在結(jié)腸癌肝臟轉(zhuǎn)移的基質(zhì)成纖維細(xì)胞中有顯著性的高表達(dá)。研究表明四氫生物蝶呤在促進血管新生和腫瘤細(xì)胞增殖中有重要作用。 本文利用已經(jīng)構(gòu)建的兩種小鼠成纖維細(xì)胞為模型，GTPCH表達(dá)組細(xì)胞命名為“GCH-tet-off”，空載體轉(zhuǎn)染組命名為“Tet-off-EV”。通過外源性添加墨蝶呤和調(diào)控GTPCH表達(dá)探究BH4的合成對這兩種細(xì)胞糖代謝以及它們成瘤性的作用。 結(jié)果顯示BH4能夠增加葡萄糖利用率和乳酸產(chǎn)量，上調(diào)LDHA、PDK1、MCT4和CAⅨ表達(dá)。BH4的合成能激活PI3K/Akt/GSK3β信號通路。此外，BH4能誘導(dǎo)成纖維細(xì)胞發(fā)生致瘤性的轉(zhuǎn)變。這些結(jié)果表明BH4促進小鼠成纖維細(xì)胞有氧糖酵解代謝表型的改變。
[Abstract]:Unlike normal differentiated cells , most of the proliferating cells and tumor cells provide energy , i.e . , the " Warburg effect " , through an aerobic glycolytic process that satisfies the synthesis and energy requirements of proliferating cells for the biosynthesis and energy of biological macromolecules . In addition , a large amount of lactic acid efflux changes the microenvironment outside the cells , creating favorable conditions for survival , growth and invasion of tumor cells . Tetrahydrobiopterin ( BH 4 ) is a cofactor of aromatic amino acid hydroxylase and nitric oxide synthase . There are two synthetic pathways : de novo synthesis and salvage synthesis . The GTPCH is a restriction enzyme in de novo synthesis . The gene chip shows significant high expression of GCH gene in stromal fibroblasts transferred from colon cancer liver . Studies have shown that tetrahydrobiopterin plays an important role in promoting angiogenesis and tumor cell proliferation . In this paper , two kinds of mouse fibroblast cells have been constructed , GTPCH expression group cells were named " GCH - tet - off " , and the empty vector transfection group was named " GCH - off - EV " . The results showed that BH could increase the glucose utilization rate and lactate production , up - regulate the expression of LDHA , PDK1 , MCT4 and CA IX . The synthesis of BH could activate the pathway of PI3尾 signaling .

【學(xué)位授予單位】：華僑大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;The role of nitric oxide in cancer[J];Cell Research;2002年Z2期

本文編號：1428046