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研究生:李婉詩
研究生(外文):Wan-Shin Lee
論文名稱:探討Amyloid-beta以及MPTP所誘發的神經細胞死亡對於電位敏感性鈣離子通道蛋白表現的調控
論文名稱(外文):Evaluating the Protein Expression of Various Voltage-Sensitive Calcium Channel in Amyloid-beta and MPTP Induced Neuronal Cell Death
指導教授:葉本和邱文慧邱文慧引用關係
指導教授(外文):Pen-Ho YehWen-Fei Chiou
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
中文關鍵詞:鈣離子通道神經細胞死亡
外文關鍵詞:Amyloid-betaMPTPcalcium channel
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本論文的目的主要在探討細胞內鈣離子濃度的平衡失調,對於Amyloid-beta以及MPTP這兩種神經毒素造成SK-N-SH細胞毒性機轉的重要性,以及長時間給予Aβ以及MPTP對於SK-N-SH細胞鈣離子通道蛋白的調控關係。除此之外,我們也選用了兩種鈣離子通道阻斷劑:nimodipine以及tetrandrine,探討它們對於Aβ以及MPTP所造成的神經傷害是否有改善的作用,以及對於鈣離子通道蛋白的影響。
從結果顯示,Aβ對於SK-N-SH細胞的毒性機轉與鈣離子之間有密切的關係,在加入Ca2+ chelator以及nimodipine、tetrandrine這兩種L型鈣離子通道阻斷劑之後,都可以有效的改善Aβ所造成的細胞死亡現象。而且Aβ會促進α1A(P/Q-type)、α1B(N-type)以及α1D(L-type)鈣離子通道蛋白的表現,而加入nimodipine及tetrandrine之後可降低α1B、α1D鈣離子通道蛋白之表現。其中α1D鈣離子通道的表現可能是造成細胞內鈣離子平衡失調的主要原因之一。另外,MPTP對SK-N-SH細胞所造成的毒性,可能不單純只和細胞內鈣離子濃度失調有關,加入Ca2+ chelator以及nimodipine、tetrandrine之後並不能改善MPTP所造成的細胞死亡現象。MPTP也會促進SK-N-SH細胞之α1A、α1B以及α1D鈣離子通道蛋白的表現,但在加入nimodipine及tetrandrine之後卻不能降低其表現量。
這些結果暗示著,nimodipine和tetrandrine除了本身對鈣離子通道的抑制作用外,在長時間給予的狀態下,可能會藉著調控鈣離子通道蛋白的表現,達到改善Aβ的神經傷害作用,這對於阿茲海默氏症的治療可能是一種新的方向。
In this study, we investigated the importance of intracellular calcium homeostasis in Amyloid beta- and MPTP-induced neuronal cell death in SK-N-SH cells. Ca2+ chelator ( EGTA: BAPTA-AM=0.5 mM : 10 μM ), nimodipine (a L-type calcium channel blocker) and tetrandrine, a non-selective calcium channel blocker which extracted from Chinese herbal Stephania tetrandra S. Moore, all decreased Aβ- but not MPTP-induced cell death. Western blot analysis for P/Q-, N- and L-type calcium channels α1-subunits demonstrated that Aβ increased the expression of neuronal α1A, α1B, and α1D subunits. Both nimodipine and tetrandrine inhibited the increased expression of α1B and α1D subunits . MPTP also upregulated the α1A, α1B, and α1D expression, however, this increasement was not influenced by nimodipine or tetrandrine. These results suggested that the mechanism of Aβ-induced neuronal cell death in SK-N-SH cells was closely associated with the elevation of intracellular calcium, whereas the calcium dyshomeostasis might not be the most important cause of the MPTP-induced neuronal cell death in SK-N-SH cells. The study also revealed that nimodipine and tetrandrine, in addition to their direct action blocking on calcium entry, they might also protect neurons from Aβ toxicity through the suppression of the calcium channel protein overexpression. A new action of nimodipine and tetrandrine may be considered in the treatment of Alzheimer’s disease.
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