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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林晉玄(Ching-Hsuan Lin) | |
dc.contributor.author | Chih-Ting Chien | en |
dc.contributor.author | 簡孜庭 | zh_TW |
dc.date.accessioned | 2021-07-11T14:34:47Z | - |
dc.date.available | 2023-07-19 | |
dc.date.copyright | 2018-07-19 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-16 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77784 | - |
dc.description.abstract | 白色念珠菌 (Candida albicans) 為常見伺機性感染人類的真菌,此真菌平常共生在人類的腸道中,當人體因老化、疾病或是藥物治療導致免疫力下降時,則容易引發嚴重的系統性感染。近年來菌株產生抗藥性的問題日益嚴重,光動力殺菌 (antimicrobial photodynamic inactivation) 便成為新興替代性治療微生物感染的方式,光動力殺菌是透過光感物質 (photosensitizer) 經特定波長光源激發後進行光化學反應,產生高活性的單態氧及自由基並毒殺細胞。將光動力療法應用於癌症細胞,所引發的細胞抵抗機制在過去已經有相當多研究,然而,以光動力殺菌治療真菌感染,其下游抵禦機制尚未明瞭。因此,本研究旨在瞭解當白色念珠菌經光感物質甲苯胺藍 (toluidine blue O, TBO) 之光動力殺菌刺激後,會啟動哪些相關抵禦氧化壓力的機制。過去研究顯示,Hog1 stress-activated protein kinase (SAPK) 訊息傳導路徑會對細胞外在環境的氧化壓力產生反應,當受到氧化壓力刺激後,Hog1 蛋白質會進行磷酸化並活化。本研究首先以西方墨點法分析,結果顯示受到光動力殺菌刺激後,Hog1 蛋白質的磷酸化程度升高,以不同濃度 TBO 進行光動力殺菌後計算菌數,發現 Hog1 路徑之突變株 (ssk1Δ、pbs2Δ、hog1Δ) 相較於野生株,其生存率顯著下降;此外,Hog1 蛋白質磷酸化位點之點突變株 (HOG1T174A、HOG1Y176F) 經光動力殺菌後生存率亦顯著降低,顯示 Hog1 蛋白質在對抗光動力殺菌的重要性。前人研究指出轉錄因子 Cap1 同樣參與白色念珠菌抗氧化壓力的訊息傳導,氧化態之 Cap1 會進入細胞核調控相關抗氧化基因表現;本研究利用即時聚合酶鏈式反應分析 CAP1 基因之表現量,結果顯示經光動力殺菌刺激後 CAP1 表現量顯著上升,以不同濃度 TBO 進行光動力殺菌後計算菌數,發現 cap1 突變株與野生株相比,其生存率同樣降低。根據上述實驗結果,顯示光動力殺菌會促使 Hog1蛋白質活化及 CAP1 表現量升高,推測 Hog1 SAPK 路徑及轉錄因子 Cap1 在白色念珠菌抵抗光動力殺菌中應扮演了重要的角色,幫助我們了解白色念珠菌面臨光動力殺菌下之防護機制。 | zh_TW |
dc.description.abstract | Candida albicans is the most important fungal pathogen afflicting humans, particularly in immunocompromised patients. However, current available antifungal drugs are limited and are ineffective against drug-resistant strains. Development of new drugs or alternative therapeutic approaches to control fungal infection is urgent and necessary. Photodynamic inactivation (PDI) is a new promising therapy for eradicating microorganism infection through combining visible light, photosensitizer and oxygen to generate reactive oxygen species (ROS). Although cytoprotective responses induced by photodynamic therapy have been well studied in cancer cells, mechanisms as to how C. albicans in response to PDI remains large unknown. In this study, we first demonstrated that PDI can induce C. albicans Hog1p activation. Deletion of SSK2, PBS2, or HOG1 caused a significantly decreased survival rate after photochemical reactions, indicating that the Hog1 SAPK pathway is required for tolerance to PDI. Furthermore, a basic leucine zipper transcription factor Cap1 regulating several downstream antioxidant genes was highly expressed during the response to PDI, and loss of the CAP1 also resulted in decreased C. albicans survival rates. Together, this study demonstrates the importance of the Hog1 SAPK and the Cap1 regulator in resistance to PDI-mediated oxidative stress in C. albicans. Understanding the mechanisms of how C. albicans responds to PDI leading to scavenge ROS will provide a great feedback for further therapeutic development to control fungal infectious diseases, particular of the skin and mucosal infections. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:34:47Z (GMT). No. of bitstreams: 1 ntu-107-R05b22032-1.pdf: 2444299 bytes, checksum: ba20b9133af50240d6254e098c8f39a5 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii 英文摘要 iv 目錄 v 圖目錄 viii 表目錄 ix 前言 1 白色念珠菌 (Candida albicans) 1 白色念珠菌氧化壓力調節適應與致病力之關聯 2 Hog1 壓力訊息傳遞路徑 (Hog1 Stress-activated protein kinase pathway) 3 Cap1 氧化壓力調控因子 (Cap1 oxidative stress regulator) 4 Hog1 與 Cap1 路徑間的調控關係 5 光動力治療發展與歷史 6 光動力治療作用機制 7 光感物質 8 光動力殺菌 (Photodynamic inactivation, PDI) 9 實驗目的 11 材料與方法 12 培養基 12 聚合酶連鎖反應 (Polymerase Chain Reaction,PCR) 12 洋菜膠體電泳分析 (Agarose gel electrophoresis) 12 DNA 片段回收 13 DNA 接合 (Ligation) 反應 13 大腸桿菌菌株轉形作用 (Transformation) 13 大腸桿菌質體 DNA 萃取 14 質體建構 15 構築 C. albicans 突變株 15 構築 cap1/cap1 突變株 16 構築 cap1/cap1::CAP1 互補株 17 光感物質 TBO 溶液之配置 17 SDS-PAGE 蛋白質電泳分析 17 SDS-PAGE 膠片配置 17 蛋白質樣本配置 18 SDS-PAGE 膠片電泳條件 18 西方墨點法 (Western blotting) 19 蛋白質轉漬 19 轉漬膜呈色 19 光動力殺菌細胞生存率測試 20 定量即時聚合酶連鎖反應 (Quantitative real time polymerase chain reaction) 20 光動力殺菌刺激條件 20 RNA 抽取 21 cDNA 反轉錄合成 22 定量即時聚合酶連鎖反應 22 結果 23 壹、探討 Hog1 路徑對於白色念珠菌抵抗光動力殺菌刺激的重要性 23 1.光動力殺菌處理會刺激 Hog1 蛋白質活化 23 2.將 SSK2、PBS2 與 HOG1基因剔除或是將 Hog1 蛋白質上的兩個磷酸化位點進行點突變以後,受光動力殺菌刺激下,菌株的存活率顯著下降 24 貳、探討 Cap1 對於白色念珠菌抵抗光動力殺菌刺激的重要性 27 1.PCR 鑑定 cap1 突變株及互補株之構築 27 2.光動力殺菌刺激會誘導 CAP1 表現量上升 28 3.CAP1 基因幫助白色念珠菌承受光動力殺菌刺激 29 參、探討 Hog1與 Cap1 兩個訊息傳導路徑間的調控關係 30 受光動力殺菌刺激下,CAP1 表現量不受 Hog1 SAPK路徑調控 30 討論 31 未來研究方向 36 圖表 38 參考文獻 53 附錄一 66 附錄二 68 | |
dc.language.iso | zh-TW | |
dc.title | 白色念珠菌 Hog1 路徑及轉錄因子 Cap1 抵抗光動力殺菌之機制探討 | zh_TW |
dc.title | Antimicrobial Photodynamic Inactivation Resistance of Candida albicans Is Modulated by the Hog1 Pathway and the Cap1 Transcription Factor | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 羅秀容(Hsiu-Jung Lo),呂俊毅(Jun-Yi Leu),張麗冠(Li-Kwan Chang),陳進庭(Chin-Tin Chen) | |
dc.subject.keyword | 白色念珠菌,光動力殺菌,氧化壓力,甲苯胺藍,Hog1,Cap1, | zh_TW |
dc.subject.keyword | Candida albicans,Hog1,Cap1,antimicrobial photodynamic inactivation (PDI), | en |
dc.relation.page | 68 | |
dc.identifier.doi | 10.6342/NTU201801474 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-07-17 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
dc.date.embargo-lift | 2023-07-19 | - |
顯示於系所單位: | 生化科技學系 |
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