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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群 | zh_TW |
| dc.contributor.advisor | Yi-Chun Wu | en |
| dc.contributor.author | 周思妤 | zh_TW |
| dc.contributor.author | Ssu-Yu Chou | en |
| dc.date.accessioned | 2021-07-11T15:01:52Z | - |
| dc.date.available | 2024-08-19 | - |
| dc.date.copyright | 2019-08-26 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Arroyo, J.D., and Hahn, W.C. (2005). Involvement of PP2A in viral and cellular transformation. Oncogene 24, 7746-7755.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78523 | - |
| dc.description.abstract | 養分攝取的多樣性深深地影響生物體內能量的穩定，不平衡的飲食內容，便可能導致一些代謝相關疾病。眾所周知，不同的營養成份會在生物體內有各種生理上的影響，然而飲食如何調控宿主的代謝機制仍有待釐清。在本研究中，我們發現餵食線蟲不同的飲食會改變線蟲脂肪的儲存、胞器數量以及動態平衡。此外，我們也發現了參與在特定的脂肪代謝以及蛋白質去磷酸化的基因對於細胞和生理過程上扮演了很重要的角色。有趣的是，在利用線蟲作為研究帕金森氏症的動物模型時，我們發現飲食可以藉由影響溶酶體清除累積蛋白質的能力，進而調控α-突觸核蛋白的累積的程度。簡而言之，我們透過許多研究來了解線蟲是如何透過飲食來調控分子與細胞機制進而造成不同的生理反應。透過釐清這些機制，可以增進我們對於飲食是如何影響肥胖以及神經退化性的帕金森氏症等疾病的知識，以及提供日後可能利用飲食進行之治療策略的一些潛在方向。 | zh_TW |
| dc.description.abstract | Diets profoundly affect energy homeostasis and the susceptibility of metabolism-related diseases. While different diets could induce distinct physiological responses, the relationship between diets and host metabolism remains elucidated. Here, we show that fat storage and organelle numbers and dynamics are altered in Caenorhabditis elegans on different diets and that genes involved in specific lipid metabolism and protein dephosphorylation play roles in these cellular and physiological processes. Interestingly, using the C. elegans Parkinson’s disease model, we found that diets can modulate the level of alpha-synuclein inclusions through lysosome-mediated clearance of protein aggregations. In brief, we have provided molecular and cellular bases for diets-mediated physiological responses, which would enhance our knowledge and provide insights for possible dietary interventions for diseases such as obesity, neurodegenerative Parkinson disease. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:01:52Z (GMT). No. of bitstreams: 1 ntu-108-R06b43007-1.pdf: 5719372 bytes, checksum: 5e17ea614552f4ee8d55d03c73a21efc (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Introduction 1 Dietary is important for homeostasis and regulates various organismal physiology 1 Post translational modification 2 PP2A and its regulation 3 Ceramide structure and metabolism 5 The storage of lipid 8 Lipid catabolism and metabolism 8 Autophagy types and mechanisms 9 C. elegans is the powerful model to investigate the lipid homeostasis and autophagy 12 Materials and methods 14 Caenorhabditis elegans strains and culture 14 Caenorhabditis elegans synchronization 15 Oil-Red-O (ORO) staining 15 RNA extraction and real-time PCR 16 let-92 double-stranded RNA generation and microinjection 17 BODIPY staining 18 Construction and microinjection 19 Western blotting 20 Ceramide inhibitor treatment 22 Fatty acid/ choline supplementation 22 Lifespan assay 23 HLH-30::GFP nuclear localization analysis 23 Microscopy visualization 24 Results 24 let-92 contributes to the diet-mediated lipid reduction in DA1877-fed worms 24 DA1877 increases ceramides level which would activate LET-92 in C. elegans 25 asm-3, a sphingomyelinase pathway gene is required for the increased ceramides in DA1877-fed worms 26 Loss of asm-3 reduced the level of ceramides in DA1877-fed worms 28 Loss of asm-3 suppressed lipid reduction on both diets 28 Ceramide plays an important role in lipid reduction in DA1877-fed worms 29 let-92 does not reduce the lipid level through inhibition of sbp-1-dependent lipogenesis on DA1877 diet 30 The autophagic flux is decreased in DA1877-fed worms and asm-3-let-92 axis seems to lead to this process 31 The decreased autophagic flux may lead to the protein aggregation and diseases 33 let-92 may affect autophagosom-lyosome fusion step in the autophagic process 34 asm-3-let-92 axis affects autophagosome-lysosome fusion step in the autophagic process 35 let-92 and asm-3 may reduce the lipid level through inducing the biosynthesis of lysosome-related organelles 36 HLH-30 does not localize to nucleus in both-diets fed worms 37 Loss of asm-3 affects the mitochondrial morphology in DA1877-fed animals 39 Discussion 41 Ceramides activate PP2A 41 DA1877-fed animals have increased PP2A activity 42 The role of let-92 in regulating the autophagy process 44 Autophagosome-lysosome fusion defect in DA1877-fed worms 44 The relationship between asm-3 and phosphatidylcholine in DA1877-fed animals 46 The possible role of microautophagy in DA1877-mediated lipid reduction 47 AMPK is not the target of PP2A, and they may be antagonized to each other 49 The roles of different bioactive molecules between bacteria diet OP50 and DA1877 50 Figures 53 Figure 1. let-92 plays an important role in regulating lipid content in DA1877-fed worms 53 Figure 2. DA1877 diet increases ceramides level in the worms 55 Figure 3. The transcriptional expression and translational expression of asm-3 are both up-regulated in DA1877-fed worms 57 Figure 4. Loss of asm-3 reduces ceramide level in DA1877-fed w orms 59 Figure 5. asm-3 mutation increased lipid content and lipid droplets size in both OP50 and DA1877-fed worms 61 Figure 6. Ceramide inhibitors increase the level of lipid content in DA1877-fed worms 63 Figure 7. Loss of sbp-1 does not suppress the increase of lipid content by let-92 RNAi 65 Figure 8. DA1877-fed worms showed decreased autophagic flux 66 Figure 9. No significant lipophagy events are found in both OP50- or DA1877-fed worms 67 Figure 10. Diet DA1877 promotes alpha synuclein inclusions in C. elegans Parkinson Disease model. 68 Figure 11. Deficiency of asm-3 or let-92 suppresses the autophagic flux reduction 69 Figure 12. asm-3 mutation and let-92 RNAi increases autophagosomes but not autolysosomes in DA1877-fed animals 72 Figure 13. let-92 RNAi and asm-3 mutant decrease the number of lysosome-related organelles in DA1877-fed worms 73 Figure 14. The mitochondrial morphology is affected by asm-3 in DA1877-fed animals 75 Figure 15. Model 76 Supplemantary figures 77 Figure S1. DA1877-fed worms have more PP2A protein 77 Figure S2. Magnified view of Pasm-3::gfp and Pasm-3::asm-3::mCherry transgenic worms 79 Figure S3. Starvation increased the autophagic flux on both diets 80 Figure S4. let-92 RNAi knockdown increases the size of LROs in DA1877-fed worms 81 Figure S5. HLH-30 localized to the intestinal nuclei in DA1877-fed worms under sodium azide treatment 83 Figure S6. Loss of hlh-30 showed different effects on the lipid content level in different diets-fed worms. 84 Figure S7. The activity of PP2A which is regulate by ceramide may not through the inhibition of SET protein 85 Figure S8. Supplementation of PC precursor, choline decreased the autophagic flux in OP50-fed worms 86 Figure S9. Total level of PC level in worms 87 Figure S10. There are more activated AMPK in DA1877-fed worms 89 Figure S11. Vitamin B12 synthesis mutant showed partial suppression on DA1877-medaited lipid reduciton 91 Figure S12. Dietary supplemetaion with palmitic acid 92 Tables 94 Table S1. Most autophagosome–lysosome fusion genes are not siginificantly differentiated expressed on different diets by RNAseq analysis 94 Supplementary: One-way ANOVA analysis 95 Supplementary: Two-way ANOVA analysis 97 References 112 | - |
| dc.language.iso | en | - |
| dc.title | 在線蟲內飲食調控胞器的數量與動態平衡 | zh_TW |
| dc.title | Regulation of organelle numbers and dynamics in C. elegans by bacterial diets | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 王昭雯;陳昌熙;金翠庭 | zh_TW |
| dc.contributor.oralexamcommittee | Chao-Wen Wang;Chang-Shi Chen;Tsiu-Ting Ching | en |
| dc.subject.keyword | 秀麗隱桿線蟲,溶?體,脂肪,脂質,飲食, | zh_TW |
| dc.subject.keyword | Caenorhabditis elegans,lysosome,fat,lipid,diet, | en |
| dc.relation.page | 119 | - |
| dc.identifier.doi | 10.6342/NTU201904030 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-08-19 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | - |
| dc.date.embargo-lift | 2024-08-26 | - |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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