Evaluating the Protein Expression of Various Voltage-Sensitive Calcium Channel in Amyloid-beta and MPTP Induced Neuronal Cell Death

• Main Authors: Wan-Shin Lee, 李婉詩
• Other Authors: Pen-Ho Yeh
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/83046118924420337477

碩士 === 國立陽明大學 === 藥理學研究所 === 92 === 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.