問題的答案無所不包論文書籍站
長庚大學 生物醫學研究所 何鴻耀所指導 林玉婷的 菸鹼醯核苷酸酶的缺乏造成粒線體與核間的訊息傳遞失調以及細胞增生的阻礙；代謝體學應用於高糖脂壓力中胰島β細胞的機制研究 （2017），提出nit recruitment關鍵因素是什麼，來自於菸鹼醯核苷酸轉氫酶、粒線體、氧化壓力、代謝體學、HIF-1α、HDAC1、胰島 β細胞、胰島素、第二型糖尿病、代謝耦合因子、choline、betaine。
而第二篇論文國立成功大學 基礎醫學研究所 吳昭良所指導 蘇鈺筑的 探討Oct4 在非小細胞肺癌腫瘤進展過程中的分子機制 （2015），提出因為有 非小細胞肺癌、Oct4、Stat1、抗細胞凋亡的重點而找出了 nit recruitment的解答。
菸鹼醯核苷酸酶的缺乏造成粒線體與核間的訊息傳遞失調以及細胞增生的阻礙；代謝體學應用於高糖脂壓力中胰島β細胞的機制研究
為了解決nit recruitment 的問題，作者林玉婷 這樣論述：
Recommendation Letter from the Thesis Advisor………………………Thesis/Dissertation Oral Defense Committee Certification…………….Acknowledgments.......………………..………………………....…........iiiChinese abstract for Topic Ⅰ……………………………..……….............ivChinese abstract for Topic Ⅱ………………………..………………........viAbstract for T
opic Ⅰ………………………………………………...…...viiiAbstract for Topic Ⅱ…………………………………………………....…xContents……………………………………………………………....…xiiList of Figures for Topic Ⅰ………………………………………….……xvList of Figures for Topic Ⅱ…………………………………….………..xviList of Tables for Topic Ⅰ……………………………………………...xviiiTopic Ⅰ:Nicotinamide nucleotide
transhydrogenase deficiency dysregulates mitochondrial retrograde signaling and impedes proliferationChapter 1 Introduction……………………………………………………11.1 Oxidative stress…………………………………………....……...11.2 Cellular defense against ROS………………………….…….…....31.3 Coenzymes - NAD(H) and NADP(H)…………………………….51.
4 Nicotinamide nucleotide transhydrogenase ………………….….71.5 HIF-1 signaling pathway………………………………………….9Chapter 2 Materials and Methods……………………………………….11Chapter 3 Results………………………………………………………..273.1 NNT deficiency causes growth slowdown of SK-Hep1 cells ……………………………………………………………….…273.2 N
NT deficiency reduces the tumorigenicity of SK-Hep1 cells…..........................................................................................273.3 Nutritional requirement departs from NNT-deficient and control cells ………..……………………………………………………283.4 Increased ATP synthesis concomitant w
ith an increase in oxidative phosphorylation in NNT-deficient cells………………....…...…283.5 NNT serves to maintain the redox homeostasis in mitochondria..293.6 Facilitated mitochondrial electron transport and anomalous mitochondrial dysfunction in NNT-deficient cells………….......313.7 NNT deficie
ncy induces anomalous cellular metabolism….......323.8 Reduction in cellular NADPH content downregulates the histone deacetylase (HDAC) activity……………………………………353.9 Reduction in HIF-1α expression and transcription of downstream genes in NNT-deficient cells……………………………...…….35Chapter 4 Discussion
………………………………………………......38References……………………………………………………………....45Figures and legends………………………………………………….....66Appendix………………………………………………….………........84Abbreviations………………………………………………………..…91Topic Ⅱ:Metabolomics study on glucose/lipid-overload-induced β cell dysfunctionChapter 1 Introduction………………………
…………………………..921.1 Type 2 diabetes and obesity……………………………………….921.2 Insulin secretion in β cells………………………………………...931.3 β cells and development of type 2 diabetes……………………….941.4 Metabolic coupling factors………………………………………..941.5 Metabolomics as functional technology………………………….96Chapter 2 Materials and
methods……………………………………….98Chapter 3 Results………………………………………………………1133.1 Glucose and lipid treatment changes physiological functions in β cells……………………………………………………………..1133.2 Chronic glucose and palmitate exposure changes energy and redox ability…………………………………………………………...1143.3 Chronic glucose/lipid exp
osure reduces insulin gene expression……………………………………………………...1153.4 Metabolic profiling of water-soluble extracts on chronic glucose and palmitate exposure in β cells………………………………1163.5 Lipidomic profiling on chronic glucose and palmitate exposure………………………………………………………..1193.6 Betaine metabolism is inv
olved in insulin release……………..120Chapter 4 Discussion…………………………………………………..123References……………………………………………………………...128Figures and legends……………………………………………………145Table……………………………………………………………………174Appendix……………………………………………………………….188Abbreviations…………………………………………………………..225 List of Figures for Topic ⅠFig
ure 1 NNT deficiency reduces proliferation and tumorigenesis of hepatoma. 66Figure 2 Effect of glucose and glutamine on proliferation of SK-shNNT and SK-Sc cells. 68Figure 3 NNT deficient cells show distinct metabolic activities. 70Figure 4 NNT deficiency causes disturbance in pyridine aden
ine dinucleotide pools. 72Figure 5 NNT deficiency enhances ΔΨm, and sensitizes rotenone. 74Figure 6 NNT deficiency reduces the flux of TCA cycle. 75Figure 7 Changes in amino acids in SK-shNNT and SK-Sc cells. 77Figure 8 Reduction in cellular NADPH content downregulates the HDAC activity
78Figure 9 NNT deficiency causes reducing HIF-1α expression and its transcription of downstream genes 80Figure 10 A proposed model of NNT in the physiological roles of hepatoma cells. 82List of Figures for Topic ⅡFigure 1 Exogenously added glucose increases β cell growth and GSIS in a conce
ntration-dependent manner………………………………145Figure 2 Free fatty acid causes lipid accumulation, cell death and reduced insulin secretion in NIT-1 cells…………………………….147Figure 3 High concentration of glucose and palmitate exposure increases ATP and ADP levelｓ but reduced ATP/ADP ratio in NIT-1 cells…………………
……………………………………………....149Figure 4 High concentration of glucose and palmitate exposure changes pyrimidine nucleotide metabolism in NIT-1 cells………………….151Figure 5 High concentration of glucose and palmitate exposure increases insulin gene expression in NIT-1 cells…………………...152Figure 6 High concentrati
on of glucose and palmitate exposure increases insulin production in NIT-1 cells…………………………153Figure 7 Base peak chromatograms of water extract of NIT-1 cells..154Figure 8 Orthogonal projections to latent structures discriminant analysis (OPLS-DA) of water-soluble metabolites in NIT-1 cells….155Figur
e 9 Pathways analysis of water-soluble metabolites is involved in chronic glucose and lipid exposure…………………………………156Figure 10 Metabolic changes of purine biosynthesis response to chronic glucose/palmitate exposure…………………………………………158Figure 11 Metabolic changes of glutathione and glyoxalase system res
ponse to chronic glucose/palmitate exposure……………………159Figure 12 Metabolic changes of TCA cycle response to chronic glucose/palmitate exposure………………………………………...161Figure 13 Target metabolic changes of TCA cycle response to chronic glucose/palmitate exposure………………………………………...162Figure 14 Metabolic cha
nges of betaine and methionine metabolism response to chronic glucose/palmitate exposure…………………...164Figure 15 Base peak chromatograms of lipid extract of NIT-1 cells...165Figure 16 Orthogonal projections to latent structures discriminant analysis (OPLS-DA) of water-soluble metabolites in NIT-1 cell
s...166Figure 17 Combination of glucose and palmitate exposure increases insulin secretion but only chronic glucose exposure doesn’t enhance insulin secretion in NIT-1 cells……………………………………168Figure 18 Metabolic changes of choline/betaine and methionine cycle response on chronic glucose/palmitate expo
sure during GSIS……169Figure 19 Betaine supplement increased insulin secretion during GSIS, and enhanced turnover of methionine cycle……………………….172 List of Tables for Topic ⅡTable 1 List of significant compounds in water-soluble metabolic profile of chronic glucose and palmitate exposure…………………..174Ta
ble 2 Total 11 significant pathway in water-soluble metabolic profile of chronic glucose and palmitate exposure…………………..……...182Table 3 List of significant compounds in lipid-soluble metabolic profile of high concentration of glucose and palmitate exposure………..….184
探討Oct4 在非小細胞肺癌腫瘤進展過程中的分子機制
為了解決nit recruitment 的問題，作者蘇鈺筑 這樣論述：
近年來，非小細胞肺癌的發生率正快速地增加中。由於非小細胞肺癌的預後非常差，因此藉由了解肺癌進展的分子機制，進而制定出有效的治療方法是當務之急。在腫瘤的進展過程中，惡性轉型的腫瘤細胞破壞組織內的恆定性，並發展出對抗細胞凋亡（apoptosis）的機制而不斷增生。此外，透過抗凋亡逃避細胞死亡的方式也造成治療效果降低與較差的預後結果，因此需要深入探討腫瘤細胞的抗凋亡機制，並從中找到新穎治療標的。根據過去的研究指出，Oct4與Stat1蛋白均在非小細胞肺癌中有過量表現的情形，並參與在細胞抗凋亡的機制中。本研究目的為探討Oct4在非小細胞肺癌中，是否透過促進Stat1的表現進而抑制細胞凋亡的進行。我們
利用54個臨床非小細胞肺癌檢體分析Oct4與Stat1的表現量，結果顯示Oct4與Stat1表現量呈現正相關，而且高度表達的Oct4與Stat1更與病人較差的預後有關聯性。接著，經由啟動子活性分析與染色質免疫沉澱證明，Oct4透過直接結合至Stat1啟動子來增加Stat1的表現量。另一方面，Stat1的下游基因Mcl-1也可受到Oct4的調控而增加表現量。除此之外，若在Oct4過量表現的細胞中抑制Stat1的表現，可以有效增加細胞對於化療藥物cisplatin的敏感性。另外在動物實驗中也發現過量表現Oct4會增加Stat1的表現量並促進腫瘤細胞的生長，而在抑制Stat1的表現後則會減緩Oct4
所誘導的腫瘤生長。綜合以上的實驗結果說明Oct4經由調控Stat1的表現而參與在抗細胞凋亡的機制中，並進一步影響非小細胞肺癌病患的預後。