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研究生:莊侑龍
研究生(外文):Yu Long Chuang
論文名稱:蜜蜂老化與能量利用之研究
論文名稱(外文):Aging dependent energy utilization in honeybee (Apis mellifera)
指導教授:徐錦源徐錦源引用關係
指導教授(外文):C. Y. Hsu
學位類別:碩士
校院名稱:長庚大學
系所名稱:生物醫學研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
論文頁數:100
中文關鍵詞:老化能量代謝能量利用
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老化是一種複雜的生理現象,普遍發生在生物體內。近年來在延緩老化的研究中發現代謝效率有增加的現象,因此代謝的相關機制可能與老化的進程有關。以蜜蜂作為老化模式動物的能量代謝研究並不多,因此我們想研究蜜蜂在年輕或老年時能量利用的情況。本篇研究指出,粒線體的數量、citrate synthase活性和電子傳遞鏈蛋白的表現量是隨著年紀增加而增加;粒線體膜電位差、ATP量、NAD+和NAD+/NADH ratio是隨著年紀增加而降低;在UCP2和NADH量則是沒有差異,顯示年輕工蜂的代謝效率優於老年工蜂。年輕工蜂代謝效率高是因為能量轉移偏向脂質氧化代謝,且不是經由抑制pyruvate進入粒線體來啟動。在細胞降解系統方面,結果顯示Lysosome enzyme活性、mTOR磷酸化會隨著年紀增加而增加,而LAMP2、LC3的量和proteasome活性隨著年紀增加而減少,顯示細胞內修復系統在年輕工蜂有較佳的效率。整個系統的啟動,是由NAD+活化SirT1,SirT1接著活化AMPK,AMPK則是會去抑制mTOR引發Autophagy,並促進PPAR-alpha的活化,啟動脂質氧化代謝,使代謝效率增加。總體而言,蜜蜂在年輕時有較高的能量代謝效率,並有較活躍的蛋白質合成與降解作用,可作為延緩老化研究的參考依據。
Aging, which generally occurs in organism, is a complex physiological phenomenon. Recently, we found the increasing metabolic efficiency in the retarding aging research; that is, the mechanism of metabolism might have some relationship with aging. There aren’t many studies using honey bees as the aging animal model of energy metabolism, so we try to observe the energy utilization on the newly eclosed and old bees. In this study, mitochondria density, citrate synthase activity and expression of electron transport chain protein increase with age; on the other hand, mitochondria membrane potential, the quantity of ATP and NAD+, and the NAD+/NADH ratio decrease with age; otherwise UCP2 and the quantity of NADH have no relationship with age. The above evidence shows the metabolic efficiency of newly eclosed bees is better than the old ones. It's because the fatty acid oxidation is turned on and it’s not the result of inhibiting pyruvate from entering mitochondria. In the study of cellular degradation system, acid phosphatase activity and the quantity of phospho-mTOR increase with age; however the quantity of LAMP2, LC3 and proteasome activity decrease with age. It shows that cellular degradation system has better efficiency in newly bees. To start the whole system, NAD+ activates SirT1; then SirT1 activates AMPK. Activated AMPK inhibits mTOR function from inducing autophagy, and promotes PPAR-alpha activation to switch on fatty acid oxidation raising the metabolic efficiency. Overall, newly eclosed bees, which have better metabolic efficiency that activates protein synthesis and cellular degradation, can be taken as the reference of retarding aging study.
目錄
指導教授推薦書
論文口試委員會審定書
長庚大學授權書………………………………………………….iv
致謝…………………………………………………………………v
中文摘要…………………………………………………………..vi
英文摘要………………………………………………………….vii
目錄……………………………………………………….……. viii
圖表目錄…………………………………………………………..xi
第一章:序論……………………………………………………….1
1.1老化現象……………………………………………………….1
1.1.1 自由基理論……………………………………….1
1.1.2 長壽基因理論…………………………………… 2
1.2細胞能量利用…………………………………………….…..4
1.3 能量代謝與老化……………………………………………..….5
1.3.1 個體大小、呼吸速率與壽命…………………………...5
1.3.2 飲食限制與抗老化……………………………………...7
1.3.3 環境溫度與抗老化…………………………………….10
1.4 細胞降解系統……………………………………………… 11
1.4.1 蛋白質降解系統……………………………….. 11
1.4.2 自噬作用…………………………………………12
1.5模式動物-蜜蜂…………………………………………….…13
第二章:研究目的………………………………………………..15
第三章:實驗材料方法…………………………………………..16
3.1 Sample的製備…………………………………………….…16
3.2 SA--gal analysis…………………………..…………………..16
3.3 Lipofuscin granules…………………………………………….16
3.4 Mitichondrial density………………………………………..…16
3.5 Mitochondral membrane potential (△ψm)………………...……17
3.6 ATP amount…………………………………………………….17
3.7 Citrate synthase activity………………………………………...17
3.8 NAD+/NADH ratio………………………..…………………..18
3.9 β-hydroxyacyl-CoA dehydrogenase activity assay……………… 19
3.10 Carnitine palmitoyltransferase II activity assay…………………..19
3.11 Pyruvate dehydrogenase activity assay……………………………19
3.12 NEFA assay………………………………………………………..20
3.13 PAS stain…………………………………………………………...20
3.14 Lysosome activity………………………………………………….20
3.15 20S proteasome activity…………………………………………..21
3.16 MDC stain………………………………………………………….22
3.17 Western blotting…………………………………………………..22
3.18 統計方法………………………………………………………….23
第四章: 數據結果……………………………………………….25
4.1蜜蜂隨年紀增長而老化…………….……………………...25
4.2蜜蜂隨年紀增長所改變的能量利用效率………………….…..25
4.3年輕工蜂能量利用轉移偏向使用Fatty acid oxidation………....28
4.4細胞內生合成……………………………………….…………30
4.5細胞降解系統…………………………………………………..31
第五章: 結果討論………………………………………………. 33
第六章:結論…………………….…………………….………….50
參考文獻……………………….………………………………...51
圖表……………………………………..……………………………....67

圖表目錄
圖一. 實驗蜂之外觀比較…………………………………...………… 67
圖二. SA-β-gal分析…………………………………………...………..68
圖三. Lipofuscin granules分析…………………………………………69
圖四. Mitochondria density分析…………………………………….…70
圖五. Mitochondria membrane potential分析…….………………...….71
圖六. ATP和ATP synthase分析……….………….…………………...73
圖七. Uncoupling protein 2分析……………………………………….74
圖八. Citrate synthase activity分析…………………………………….75
圖九. NADH和NADH dehydrogenase分析……………………........ 76
圖十. -oxidation分析………………………………………………….78
圖十一. Carnitine palmitoyltransferase II分析…………………...……79
圖十二. Pyruvate dehydrogenase分析………………………..………..80
圖十三. PPAR和free fatty acid分析………………………………..81
圖十四. AMPK和SirT1分析…………………..…………………..….82
圖十五. eIF4E和Fatty acid synthase 活性…………………….…..….83
圖十六. Glycogen PAS染色分析…………….……………………..….84
圖十七. LC3、pmTOR和mTOR分析……………………………..…85
圖十八. Lysosome分析……………………………………………..….86
圖十九. Protein degradation分析……………………………….…..….87
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