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

  更多相關文章： 四氫生物蝶呤 葡萄糖 糖酵解 成纖維細胞

【摘要】：與正常分化的細胞不同，多數增殖細胞和腫瘤細胞通過有氧糖酵解的方式為細胞生理過程提供能量，即“Warburg效應”。這種快速有效的代謝重編程滿足了增殖細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胞外的微環(huán)境，為腫瘤細胞的存活、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果顯示，，GCH基因在結腸癌肝臟轉移的基質成纖維細胞中有顯著性的高表達。研究表明四氫生物蝶呤在促進血管新生和腫瘤細胞增殖中有重要作用。 本文利用已經構建的兩種小鼠成纖維細胞為模型，GTPCH表達組細胞命名為“GCH-tet-off”，空載體轉染組命名為“Tet-off-EV”。通過外源性添加墨蝶呤和調控GTPCH表達探究BH4的合成對這兩種細胞糖代謝以及它們成瘤性的作用。 結果顯示BH4能夠增加葡萄糖利用率和乳酸產量，上調LDHA、PDK1、MCT4和CAⅨ表達。BH4的合成能激活PI3K/Akt/GSK3β信號通路。此外，BH4能誘導成纖維細胞發(fā)生致瘤性的轉變。這些結果表明BH4促進小鼠成纖維細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 .

【學位授予單位】：華僑大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965

【參考文獻】

相關期刊論文 前1條

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

本文編號：1428046