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    題名: 棕櫚酸可藉由蛋白質棕櫚酸化作用促使SH-SY5Y細胞週期停滯及細胞凋亡
    Palmitic acid induced neuron cell cycle arrest and apoptosis through protein palmitoylation in SH-SY5Y cells
    作者: 蕭詠瑄
    Hsiao, Yung-Hsuan
    貢獻者: 保健營養學研究所
    林士祥
    關鍵詞: 棕櫚酸;內質網壓力;阿茲海默症;細胞凋亡;細胞週期停滯
    palmitic acid;endoplasmic reticulum stress;neurodegenerative disease;apoptosis;cell cycle arrest
    日期: 2012-06-17
    上傳時間: 2018-10-08 13:39:48 (UTC+8)
    摘要: 流行病學研究顯示,含高量飽和脂肪酸的飲食型態,會增加罹患神經退化性疾病的風險,尤其是阿茲海默症。並且,阿茲海默症患者腦中,飽和脂肪酸含量也較正常人高。另外,給予動物高飽和脂肪酸飲食,確實也會引發認知功能障礙、神經退化性疾病相關病理特徵,及神經細胞的凋亡。因此,本次研究目的,為探討飽和脂肪酸造成神經細胞凋亡的可能機制。本試驗以人類神經纖維母細胞株 SH-SY5Y為神經細胞模式,給予棕櫚酸及油酸的處理,觀察細胞週期的變化及影響細胞週期的可能路徑,並利用多酚類、維生素C等抗氧化劑、蛋白質激酶C抑制劑,及棕櫚酸化作用抑制劑,觀察棕櫚酸造成神經細胞凋亡的路徑。結果發現,棕櫚酸可引發神經細胞型態的改變,並造成神經細胞內質網壓力顯著增加,使神經細胞週期停滯在G2/M期,進而引發細胞凋亡。並且,棕櫚酸主要是透過蛋白質棕櫚酸化作用,造成神經細胞內質網壓力增加、G2/M期停滯及細胞凋亡。同時,棕櫚酸也可促使beta-secretase蛋白質表現量的增加,並導致類澱粉樣蛋白質的堆積。結論,飽和脂肪酸,尤其是棕櫚酸,可經由蛋白質棕櫚酸化作用,使神經細胞出現內質網壓力,導致細胞週期停滯在G2/M期,同時伴隨類澱粉樣蛋白質的堆積,引發神經細胞凋亡。
    Epidemiological studies suggested that high fat diet is one of the notable risk factors of neurodegenerative disease (NDs), especially Alzheimer’s disease (AD). The degree of fatty acid saturation is also critical point in AD development. Dietary saturated fatty acids (SFAs) stimulate brain to uptake SFAs from plasma through the blood brain barrier. The elevation of SFAs, especially palmitic acid (PA), may exacerbate cellular damages directly in the brain. It is also noteworthy that type 2 diabetes is a risk factor of AD development, which is characterized by an elevation of PA in blood. In the present study, we examined the effects of chronic palmitic acid exposure on the cell cycle of SH-SY5Y human neuroblastoma cells. We found that chronic palmitic acid exposure induced significant G2/M arrest in the neuronal cells through endoplasmic reticulum (ER) stress. Furthermore, the G2/M arrest and ER stress were inhibited by the palmitoylation inhibitor. These findings suggested that palmitic acid induced ER tress, G2/M arrest and neuronal cell apoptosis through palmitoylation.
    描述: 碩士
    指導教授-林士祥
    委員-沈賜川
    委員-陳玉華
    資料類型: thesis
    顯示於類別:[保健營養學系暨研究所] 碩博士論文

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