Yurinskaya M M, Mit'kevich V A, Barykin E P, Garbuz D G, Evgen'ev M B, Makarov A A, Vinokurov M G
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia.
Mol Biol (Mosk). 2015 Nov-Dec;49(6):1030-4. doi: 10.7868/S0026898415060233.
Neuronal cell death in Alzheimer's disease is associated with the development of oxidative stress caused by the reactive oxygen species (ROS), which can be generated as a result of the effect of beta-amyloid peptides. One of the sources of ROS is hydrogen peroxide, inducing the apoptosis and necrosis of neural tissue cells. The mechanism of hydrogen peroxide apoptotic action includes launching signaling pathways that involve protein kinases PI3K, p38MAPK, JNK and ERK. Oxidative stress leads to increased synthesis of heat-shock proteins in the cells including HSP70. It was shown that the exogenous HSP70 could reduce generation of ROS in cells. In this study, we determined how HSP70 affected apoptosis and necrosis in human neuroblastoma cells SK-N-SH, induced by hydrogen peroxide and β-amyloid peptide Aβ(1-42). It was shown that HSP70 reduces the cytotoxic effects of hydrogen peroxide and beta-amyloid, and protein kinases PI3K and JNK play an important role in the mechanism of HSP70 protective effect on the peroxide induced apoptosis in SK-N-SH cells.
阿尔茨海默病中的神经元细胞死亡与活性氧（ROS）引起的氧化应激发展相关，ROS可由β-淀粉样肽的作用产生。ROS的来源之一是过氧化氢，它会诱导神经组织细胞的凋亡和坏死。过氧化氢凋亡作用的机制包括启动涉及蛋白激酶PI3K、p38MAPK、JNK和ERK的信号通路。氧化应激导致细胞内热休克蛋白的合成增加，包括HSP70。研究表明，外源性HSP70可减少细胞中ROS的产生。在本研究中，我们确定了HSP70如何影响过氧化氢和β-淀粉样肽Aβ(1-42)诱导的人神经母细胞瘤细胞SK-N-SH中的凋亡和坏死。结果表明，HSP70可降低过氧化氢和β-淀粉样蛋白的细胞毒性作用，蛋白激酶PI3K和JNK在HSP70对SK-N-SH细胞中过氧化氢诱导的凋亡的保护作用机制中起重要作用。
