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研究生:林依靜
研究生(外文):Yi-Ching Lin
論文名稱:第六型膠原蛋白對於紫外線引發的神經細胞凋亡之保護作用
論文名稱(外文):Protective Effect of Collagen VI Against Apoptosis Due to UV-induced Damage in Neuron
指導教授:鄭菡若
指導教授(外文):Irene Han-Juo Cheng
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:腦科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:67
中文關鍵詞:膠原蛋白紫外線神經細胞
外文關鍵詞:Collagen VIUVNeuron
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許多神經退化性疾病,如阿茲海默症,最主要的危險因子是老化。而老化,就分子的角度而言,原因之一是氧化壓力所引起的。活性氧化物(reactive oxygen species, ROS)是具有高度氧化力的分子。當細胞內的ROS過量時,會對DNA、蛋白質和細胞膜脂質造成傷害。先前的研究指出,大腦中第六型膠原蛋白的濃度上升,有助於神經細胞抵抗乙型類澱粉蛋白所引發的細胞凋亡。因此,本實驗想探討第六型膠原蛋白是否也能保護細胞免於DNA 損傷所引起的細胞凋亡。使用初代腦皮質細胞培養後,接受UV照射處理,用以分析第六型膠原蛋白的表現量及對細胞的影響,並用TUNEL試驗以及MTT試驗來偵測細胞死亡率。其所引發的訊息傳遞分子的改變,則由西方墨點法及使用抑制劑的方式來分析。結果發現,經過UV照射處理的神經細胞,會提高第六型膠原蛋白mRNA的表現量,且在培養基中外加高濃度第六型膠原蛋白能保護神經細胞,抵抗UV所引發的細胞凋亡。而這樣的保護機制與Akt及JNK訊息傳遞路徑有關。因此,這樣的結果暗示,在面對DNA損傷所引起細胞凋亡時,第六型膠原蛋白有可能是神經細胞自我保護的機制之一。
The major risk factor of many neurodegenerative disorders such as Alzheimers’ disease is aging. One of the explanations on how aging occurs at the molecular level is the oxidative stress hypothesis. Reactive oxygen species (ROS) are highly oxidative molecules that damage DNA, protein and membranous lipids. Previous research indicated that increase of collagen VI can protect neurons against amyloid-�� induced cell death. In this study, I tried to determine whether collagen VI can also protect neuron against apoptosis due to UV damage. Primary cortical neuronal culture was exposed to UV to determine the alternation of collagen VI expression. Percent cell death under different treatments was determined by TUNEL assay, MTT assay and morphology. The involvement of different signaling molecules was determined by Western blotting and inhibitor treatments. I found that the mRNA level of collagen VI increases after UV irradiation. High level of collagen VI in the culture media can protect neurons from UV-induced apoptosis. This protective effect may mediate through Akt/JNK pathway. Therefore, my result indicated that increasing of collagen VI may be a self-protective mechanism of neuron against DNA damage.
Index .......................1
致謝 ........................2
Abstract ...................3
中文摘要 ...................4
Introduction ...............5
Hypothesis .................14
Materials and Methods ......16
Results ....................23
Discussion .................47
Conclusions ................52
Tables .....................54
Appendix ...................55
Reference ..................66
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