Lee Jong-Sun, Kim Jeong-Yub, Kim Hee-Jin, Kim Jeong Cheol, Lee Jae-Seon, Kim Nam, Park Myung-Jin
Division of Radiation Cancer Research, Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Nowongil 75, Nowon-Gu, Seoul 139-706, Korea.
Department of Pathology, College of Medicine, Korea University, Seoul 136-705, Korea.
J Radiat Res. 2016 Nov;57(6):620-626. doi: 10.1093/jrr/rrw040. Epub 2016 Jun 20.
Alzheimer's disease (AD) is the most common progressive and irreversible neurodegenerative disease and it is caused by neuronal death in the brain. Recent studies have shown that non-ionizing radiofrequency (RF) radiation has some beneficial cognitive effects in animal models of AD. In this study, we examined the effect of combined RF radiation on amyloid-beta (Aβ)-induced cytotoxicity in HT22 rat hippocampal neurons. Treatment with Aβ suppressed HT22 cell proliferation in a concentration-dependent manner. RF exposure did not affect cell proliferation, and also had a marginal effect on Aβ-induced suppression of growth in HT22 cells. Cell cycle analysis showed that Aβ decreased the G1 fraction and increased the subG1 fraction, indicating increased apoptosis. Accordingly, Aβ increased the annexin V/propidium iodide (PI)-positive cell fraction and the degradation of poly (ADP ribose) polymerase and caspase-3 in HT22 cells. However, RF alone and the combination of Aβ and RF did not affect these events significantly. Aβ increased reactive oxygen species (ROS) generation, thereby suppressing cell proliferation. This was abrogated by N-acetylcysteine (NAC) treatment, indicating that Aβ-induced ROS generation is the main cause of suppression of proliferation. NAC also restored Aβ-induced annexin V/PI-positive cell populations. However, RF did not have a significant impact on these events. Finally, Aβ stimulated the ataxia telangiectasia and Rad3-related protein/checkpoint kinase 1 DNA single-strand breakage pathway, and enhanced beta-site amyloid precursor protein expression; RF had no effect on them. Taken together, our results demonstrate that RF exposure did not significantly affect the Aβ-induced decrease of cell proliferation, increase of ROS production, or induction of cell death in these cells.
阿尔茨海默病（AD）是最常见的进行性和不可逆性神经退行性疾病，由大脑中的神经元死亡引起。最近的研究表明，非电离射频（RF）辐射在AD动物模型中具有一些有益的认知作用。在本研究中，我们研究了联合RF辐射对淀粉样β蛋白（Aβ）诱导的HT22大鼠海马神经元细胞毒性的影响。用Aβ处理以浓度依赖性方式抑制HT22细胞增殖。RF暴露不影响细胞增殖，对Aβ诱导的HT22细胞生长抑制也有轻微影响。细胞周期分析表明，Aβ降低了G1期比例并增加了亚G1期比例，表明细胞凋亡增加。因此，Aβ增加了膜联蛋白V/碘化丙啶（PI）阳性细胞比例以及HT22细胞中聚（ADP核糖）聚合酶和半胱天冬酶-3的降解。然而，单独的RF以及Aβ与RF的组合并未显著影响这些事件。Aβ增加活性氧（ROS）生成，从而抑制细胞增殖。N-乙酰半胱氨酸（NAC）处理可消除这种情况，表明Aβ诱导的ROS生成是增殖抑制的主要原因。NAC还恢复了Aβ诱导的膜联蛋白V/PI阳性细胞群体。然而，RF对这些事件没有显著影响。最后，Aβ刺激共济失调毛细血管扩张症和Rad3相关蛋白/检查点激酶1 DNA单链断裂途径，并增强β位点淀粉样前体蛋白表达；RF对它们没有影响。综上所述，我们的结果表明，RF暴露并未显著影响Aβ诱导的这些细胞中细胞增殖的减少、ROS产生的增加或细胞死亡的诱导。
