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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 詹智強 | |
dc.contributor.author | Yu-Lian Yu | en |
dc.contributor.author | 游宇蓮 | zh_TW |
dc.date.accessioned | 2021-05-19T17:51:57Z | - |
dc.date.available | 2022-09-08 | |
dc.date.available | 2021-05-19T17:51:57Z | - |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-03 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7741 | - |
dc.description.abstract | Infertile crescent (Ifc) 為演化上具高度保守性的脂質修飾酵素,負責在果蠅神經脂質新合成路徑中將二羥基神經醯胺(dihydroceramide, DHCer)轉變成神經醯胺(ceramide, Cer)。為瞭解ifc在神經的功能,我們於果蠅眼睛建立ifc-KO突變細胞群組(mutant clone),發現失去ifc會導致成體視神經的漸進式活性依賴退化。
為瞭解其神經退化之機制,我們以ifc-KO全感光細胞突變群組(ifc-KO whole eye clone)進行研究,發現失去ifc會導致果蠅視神經中參與光傳遞路徑的Rhodopsin 1與調控桿狀小體(rhabdomere)形成之Chaoptin堆積,但不影響發育時期Eyes shut蛋白的分佈。由於ifc參與神經脂質新合成路徑,因此我們在群組分析中檢測失去ifc是否影響脂質恆定,發現在ifc-KO感光細胞突變群組分析中有脂質堆積,且脂噬作用提昇。前人研究發現光刺激會活化Rac1導致NADPH oxidase (Nox)產生ROS,而我們觀察到失去ifc後ROS提升,並且透過藥物抑制Nox後,ROS下降,以及保護神經免於光依賴退化。此外,我們亦發現Ifc位於Rab4相關之外吐小體(exosome),並可於視神經細胞中觀察到錐細胞或色素細胞過表達之Ifc-mCherry蛋白,推測Ifc可離開製造細胞產生細胞非自主機制(cell non-autonomously)之作用,並參與調控exosome分泌作用。 此研究除了瞭解ifc於視神經活性依賴退化中扮演的角色,也探討細胞外吐作用的調控,除對ifc之功能更加瞭解外,或許也能作為神經細胞與其他細胞溝通的基礎。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-05-19T17:51:57Z (GMT). No. of bitstreams: 1 ntu-106-R04441009-1.pdf: 3295158 bytes, checksum: bd3b586b2f145c80c9d2b9931e4f2ad5 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 摘要 i
Abstract ii 目錄 iv 第一章 實驗背景 1 1.1神經脂質與細胞膜狀胞器運輸機制 2 1.2 Dihydroceramide desaturase於哺乳類細胞及果蠅中之功能 5 1.3細胞內膜運輸與視神經細胞活性依賴退化 6 1.4光刺激與ROS 9 1.5 Rab與外吐小體 11 第二章 實驗材料與方法 14 2.1 果蠅株及培養方法 15 2.2 果蠅食物培養基製備 16 2.3 視神經電位紀錄(Electroretinogram) 16 2.4 免疫螢光染色與共軛焦顯微鏡(Confocal microscope)使用 17 2.5 免疫染色抗體清單(IHC Antibody List) 19 2.6 群組分析(Clonal analysis) 20 2.7 果蠅餵食藥劑實驗製備 21 第三章 實驗結果 22 3.1在果蠅視神經失去ifc造成漸進式活性細胞退化 23 3.2在果蠅視神經失去ifc造成脂噬作用增加 23 3.3在果蠅視神經失去ifc會導致Rh1堆積在Atg8a相關胞器 24 3.4在果蠅視神經失去ifc會造成Chaoptin堆積,但不影響Eyes shut 25 3.5減少Rh1表現會恢復失去ifc後產生的漸進式神經退化 25 3.6餵食Apocynin抑制NOX會恢復ifc-KO造成的神經退化與降低ROS 25 3.7果蠅神經膠細胞表現Ifc-mCherry會出現在視神經細胞 26 3.8 Ifc與內生性Rab4共位 26 3.9在果蠅三齡幼蟲眼碟細胞外之Ifc位於Rab4-EYFP相關之囊泡 27 3.10 Ifc位於Flo2-EYFP相關之囊泡 27 3.11果蠅三齡幼蟲眼碟細胞之Ifc-mCherry與mCD8::GFP可離開製造細胞 27 第四章 實驗討論 29 4.1 ifc為細胞非自主機制及其在神經細胞與神經膠細胞之功能 30 4.2 ifc與細胞膜上的蛋白運輸之調控 30 4.3 失去ifc產生的活性依賴退化與Rac1-NOX pathway之關係 32 4.4 ifc與Rab4調控之外吐小體的關係 33 第五章 未來實驗方向 34 5.1探討在視神經細胞或神經膠細胞失去ifc對果蠅視神經存活之影響 35 5.2探討ifc與rab4調控的外吐小體之交互作用 35 5.3探討ifc對果蠅視神經中外吐小體生成與分泌的調控 36 5.4 ifc是否影響lipid raft上之Flo2蛋白造成細胞膜內運輸與內吞作用失常 38 第六章 實驗圖表 39 Fig. 1 在果蠅視神經失去ifc造成漸進式活性細胞退化 40 Fig. 2 在果蠅視神經失去ifc造成脂噬作用增加 41 Fig. 3 在果蠅視神經失去ifc會造成Rh1堆積在Atg8a相關胞器 42 Fig. 4 在果蠅視神經失去ifc會造Chaoptin堆積,但不影響Eyes shut 43 Fig. 5 減少Rh1表現會恢復失去ifc後產生的漸進式神經退化 44 Fig. 6 餵食Apocynin抑制NOX會恢復ifc-KO產生的漸進式神經退化與降低ROS 45 Fig. 7果蠅神經膠細胞表現Ifc-mCherry會出現在視神經細胞 46 Fig. 8 Ifc與內生性Rab4共位 47 Fig. 9果蠅三齡幼蟲眼碟細胞外之Ifc位於Rab4-EYFP相關之囊泡 48 Fig. 10 Ifc位於Flo2-YFP相關之囊泡 49 Fig. 11果蠅三齡幼蟲眼碟細胞外之Ifc-mCherry與mCD8::GFP可離開表現細胞 50 第七章 參考文獻 51 | |
dc.language.iso | zh-TW | |
dc.title | infertile crescent (ifc) 於神經中調控細胞內膜運輸與外吐小體分泌 | zh_TW |
dc.title | infertile crescent (ifc) regulates intracellular trafficking and exosome secretion for neuronal maintenance | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳光超,劉雅雯 | |
dc.subject.keyword | 神經脂質,視神經活性依賴退化,外吐小體, | zh_TW |
dc.subject.keyword | Sphingolipid,light dependent neurodegeneration,exosome, | en |
dc.relation.page | 63 | |
dc.identifier.doi | 10.6342/NTU201702435 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2017-08-03 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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