- 學位論文
1, 25(OH)2D3 透過提高 GDNF 表現量活化 PI3K/Akt 減少細胞凋亡和 降低 Tau 過磷酸化以減少 Aβ 對細胞造成的傷害
1, 25(OH)2D3 against the toxicity of Aβ through increasing the protein expression of Glial cell line derived neurotrophic factor and following by activating Phosphatidylinositol 3 kinase / protein kinase B, decreasing cell apoptosis and tau protein hyperphosphorylation.
摘要
阿茲海默症為常見的失智症類型，主要病因為細胞內的 tau 過磷酸 化和 Aβ (Amyloid β) 累積過多，使得大腦神經元失去正常功能而凋亡。 文獻顯示，過多的 tau 過磷酸化和 Aβ 會使神經元所需的神經滋養因子 分泌下降，為導致神經細胞凋亡的原因之一。在體外神經細胞實驗中， 1,25(OH)2D3 可顯著提高 Glial cell line-derived neurotrophic factor (GDNF)的表現量。GDNF 可以透過活化細胞內 phosphatidylinositol 3-kinase / protein kinase B (PI3K/Akt) 以降低 tau 過磷酸化和細胞凋亡。因此，本研究將於人類神經纖維瘤母細胞株 (Human neuroblastoma cell line, SH-SY5Y) 加入 1,25(OH)2D3 與 Aβ，觀察 1,25(OH)2D3 對 Aβ 於細胞 造成之傷害，是否具有預防及改善作用。結果顯示，在 Aβ 傷害前給予 1,25(OH)2D3 介入，與未介入 1,25(OH)2D3 組相比，可提高 GDNF 表現、 活化 PI3K/Akt、降低 tau 過磷酸化且降低細胞凋亡。在 Aβ 傷害下給予 1,25(OH)2D3 與未介入 1,25(OH)2D3 組相比，可提高 GDNF 表現、活化 PI3K /Akt、降低 tau 過磷酸化且降低細胞凋亡。綜合上述結果顯示， 1,25(OH)2D3 可透過提高 GDNF 的表現以活化 PI3K/Akt 路徑，降低 tau 過磷酸化與細胞凋亡，具有預防及改善 Aβ 對細胞造成之傷害。
並列摘要
The causes of alzheimer’s disease are accumulation of Aβ and intracellular tau protein hyperphosphorylation in brain, leading to neuron dysfunctions and cell apoptosis. The neurotrophic factors decreasing that result in cell apoptosis is caused by the accumulation of Aβ. According to the recent studies, 1,25(OH)2D3 increased the protein expression of GDNF that can support the neuron survive in primary neuron culture. In Enteric neuroblasts, GDNF active the PI3K / Akt pathway to phosphorylate Glycogen synthase kinase-3β (GSK-3β) at ser-9 position, decreasing cell apoptosis and tau protein hyperphosphorylation. The propose of this study was to investigate the neuroprotection of 1,25(OH)2D3 toward the cell treated with Aβ. We found that 1,25(OH)2D3 increased the the protein expression of GDNF,activing the PI3K /Akt pathway and decreased the cell apoptosis and tau protein hyperphosphorylation in SH-SY5Y human neuroblastoma cell which is treated with Aβ before or after 1,25(OH)2D3 treatment. 1,25(OH)2D3 can protect and ameliorate the damage caused by Aβ in SH-SY5Y human neuroblastoma cell.
參考文獻
延伸閱讀
- 許譽騰（2006）。Tanshinone IIA經由Phosphatidylinositol 3-kinase /Akt 路徑誘導血紅素氧化酵素-1而抑制脂多醣體所誘導的一氧化氮與環氧酵素-2的表現〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200715050678
- 關宇翔（2006）。探討在嗜中性白血球 CYL-26z 抑制 phospholipase D 活化，artocarpol A 促進生成超氧自由基及formyl peptide 活化phosphoinositide 3-kinase的作用機制〔博士論文，中山醫學大學〕。華藝線上圖書館。https://doi.org/10.6834/CSMU.2006.00054
- 高詩涵（2010）。Tellimagrandin II 對於巨噬細胞在酯多醣體誘導後所產生的一氧化氮及前列腺素E2的抑制〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-2408201015403900
- Delagoutte, E., & Baldacci, G. (2011). 5'CAG and 5'CTG Repeats Create Differential Impediment to the Progression of a Minimal Reconstituted T4 Replisome Depending on the Concentration of dNTPs. Molecular Biology International, 2011(), 70-83. https://doi.org/10.4061/2011/213824
- 李家榮（2008）。Part I:Effect on Gap Junction Intercellular Communication by Tributyltin Chloride (TBTC) and Triphenyltin Chloride (TPTC) in WB-F344 Rat Liver Epithelial Cells./Part II:Determination of Metal in Blood and Urine of Alloy Casting Factory Workers by Graphite-Furnace Atomic Absorption Spectrometry (GF-AAS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS).〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-0608200814035800