Varmazyar R, Noori-Zadeh A, Abbaszadeh H A, Hamidabadi H Ghasemi, Rajaei F, Darabi S, Rezaie M J, Abdollahifar M A, Zafari F, Bakhtiyari S
Bratisl Lek Listy. 2019;120(10):744-751. doi: 10.4149/BLL_2019_124.
This study was conducted to investigate the effects of Simvastatin (SIM), a member of statin family, on the cellular antioxidant system, autophagy and apoptosis in NSCs exposed to hydrogen peroxide.
Reduction in cellular oxidative stress increases the survival of neural stem cells (NSCs) after transplantation into the damaged area of the affected central nervous system.
NSCs derived from bone marrow stromal cells (BMSCs) were exposed to H2O2 (100 μM) for 48 hours after pretreatment with SIM (2 μM). Next, the expressions of the master antioxidant transcription factor, Nrf2/nuclear factor erythroid 2 (NFE2)-related factor 2, autophagy-related proteins (microtubule-associated proteins 1A/1B light chain 3B known as LC3I and LC3II and also p62/Sequestosome), and apoptosis (Bcl-2/ B-cell lymphoma 2 and Bax/BCL2 associated X protein) were analyzed.
SIM caused Nrf2 over-activation (more localizations in the cellular nucleus), reduction in reactive oxygen species (ROS), induction of autophagy (decrease in p62 expression and increase in LC3II/LC3I ratio) and inhibition of apoptosis (decrease in Bax protein and increase in Bcl-2) in NSCs exposed to H2O2-induced oxidative stress, thereby prolonging the cell viability within 48 hours at low concentration (2 μM).
SIM protects NSCs against H2O2-induced apoptosis in a pleiotropic signaling manner (Fig. 7, Ref. 35).
本研究旨在探讨他汀类药物家族成员辛伐他汀（SIM）对暴露于过氧化氢的神经干细胞（NSCs）细胞抗氧化系统、自噬和凋亡的影响。
细胞氧化应激的降低可提高神经干细胞（NSCs）移植到受影响中枢神经系统损伤区域后的存活率。
从骨髓基质细胞（BMSCs）中提取的神经干细胞（NSCs）在经辛伐他汀（2 μM）预处理后，再暴露于过氧化氢（100 μM）48小时。接下来，分析主要抗氧化转录因子Nrf2/核因子红细胞2（NFE2）相关因子2、自噬相关蛋白（微管相关蛋白1A/1B轻链3B，即LC3I和LC3II，以及p62/隔离小体）和凋亡相关蛋白（Bcl-2/B细胞淋巴瘤2和Bax/BCL2相关X蛋白）的表达。
在暴露于过氧化氢诱导的氧化应激的神经干细胞（NSCs）中，辛伐他汀导致Nrf2过度激活（更多定位于细胞核）、活性氧（ROS）减少、自噬诱导（p62表达降低和LC3II/LC3I比值增加）以及凋亡抑制（Bax蛋白减少和Bcl-2增加），从而在低浓度（2 μM）下48小时内延长细胞活力。
辛伐他汀以多效信号传导方式保护神经干细胞（NSCs）免受过氧化氢诱导的凋亡（图7，参考文献35）。
