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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53716

Title: 以小鼠神經 N2a 細胞模式探討視黃醇之細胞毒性
Studies on Cytotoxicity of Retinol in the Model of Mouse Neuron N2a Cell
Authors: Huang, Yu-Lin
黃育琳
Contributors: NTOU:Department of Food Science
國立臺灣海洋大學:食品科學系
Keywords: 維生素 A;視黃醇;細胞毒性;細胞凋亡
vitamin A;retinol;cytotoxicity;apoptosis
Date: 2019
Issue Date: 2020-07-03T08:43:06Z
Abstract:   維生素 A 為人類的生殖、視力及成長等生理功能所必需的化合物,而視黃醇 (retinol) 被視為類維生素 A (retinoids) 的母體分子,為細胞早期成長過程中調節細胞週期和分化的必需因子。然而過量攝食維生素 A 可能會導致急性或慢性中毒,急性中毒通常發生於食用大型魚類之肝臟如笛鯛魚或石斑魚肝,症狀包括噁心、頭痛、暈眩、視力模糊及肌肉不協調等;慢性中毒則通常發生於長期食用過量維生素 A 補充品,症狀包括骨骼異常、脫皮、指甲脆化、脫髮、發燒、嗜睡及肝腫大等,顯然食用過量維生素 A 導致中毒之風險仍不容小覷。本研究第一章採用小鼠神經纖維瘤母細胞 (mouse neuroblastoma cell; N2a cell) 作為模式,暴露濃度範圍為 0~28 μM 視黃醇,探討細胞所受之影響,包括以細胞存活率分析視黃醇半最大抑制濃度 (half maximal inhibitory concentration; IC50),及觀察細胞外觀型態變化以瞭解細胞毒性,測定各項生物活性指標如乳酸去氫酶 (lactate dehydrogenase; LDH)、肌酸激酶 (creatine kinase; CK) 與腺苷三磷酸酶 (adenosine triphosphatase; ATPase) 活性共三項;第二章則延續前一章之結果,探討視黃醇作用於 N2a 細胞是否會造成其凋亡,包括觀察細胞的氧化壓力變化、粒腺體損傷程度、染色體 DNA 損傷程度與 caspase 3/7 活性測定。結果顯示暴露視黃醇大於 22 μM 顯著對 N2a 細胞產生顯著毒性效應,包括細胞存活率降低、型態改變、LDH 釋放量與 CK 活性增加,進而建立視黃醇之專一細胞毒性檢測指標。細胞凋亡相關特徵結果為活性氧物質 (reactive oxygen species ; ROS) 產量增加、粒腺體膜電位與 ATP 含量降低,及 DNA 出現片段化之現象增加,顯示視黃醇確實會誘導哺乳類動物神經腫瘤細胞凋亡。我國所訂定之視黃醇 RDA 標準攝食劑量遠低於本研究之細胞毒性劑量,依其劑量服用不會發生毒作用之風險,但生活中仍應避免攝食到大型魚類之肝臟,或是過度補充維生素 A,以防止罹患維生素 A 過多症之機會。此外,從現代腫瘤學角度來看,視黃醇亦具有作為腫瘤治療應用上之潛力。
Vitamin A is an essential compound for human physiological functions such as reproduction, vision and growth, and retinol is considered to be the parent molecule of retinoids, regulating cell cycle and differentiation during early cell growth. However, excessive intake of vitamin A may cause acute or chronic poisoning. Acute poisoning usually occurs in consumption of the livers of large fish such as snapper or grouper liver. Symptoms include nausea, headache, dizziness, blurred vision and muscle imbalance. Chronic poisoning usually occurs in long-term consumption of excess vitamin A supplements. Symptoms include abnormal bones, skin peeling, nail embrittlement, hair loss, fever, lethargy, and hepatomegaly. Obviously, the risk of poisoning caused by excess consumption of vitamin A is not to be underestimated. In the first chapter of this study, mouse neuroblastoma cell (N2a cell) was used as a model and exposed 0-28 μM retinol to investigate the effects of retinol on cells, including half maximal inhibitory concentration (IC50), cell viability and morphology. Biological activity of various indicators were also investigated such as lactate dehydrogenase (LDH), creatine kinase (CK) and adenosine triphosphatase (ATPase). The second chapter investigated whether retinol induced to apoptosis on N2a cell, including change in oxidative stress, mitochondria dysfunction, degree of chromosomal DNA damage and caspase 3/7 activity. The results show the cells exhibited significant toxic response when retinol level was more than 22 μM, including decreasing cell viability, altering morphology, increasing LDH release and CK activity. The characteristics of cell apoptosis are increasing reactive oxygen species (ROS) production, fragmentation of DNA and caspase 3/7 activity, and decreasing mitochondrial membrane potential and ATP content. Therefore, excess dose of retinol can induce apoptosis of mammalian neuronal tumor cells. Although the standard dose of recommended dietary allowances (RDA) of retinol is much lower than the cytotoxic dose of this study, people should avoid eating the big fish liver or excessive intaking vitamin A supplements. In addition, from the perspective of modern oncology, retinol also has potential as a therapeutic application for cancer.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010632015.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53716
Appears in Collections:[食品科學系] 博碩士論文

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