Protective effects of butein on corticosterone-induced cytotoxicity in Neuro2A cells
Protective effects of butein on corticosterone-induced cytotoxicity in Neuro2A cells
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DOI：
10.1016/j.ibror.2020.02.002
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发表时间：
2020-06-01
期刊：
影响因子：
2.6
通讯作者：
Daikoku, Tohru
中科院分区：
文献类型：
--
作者：
Ohmoto, Masanori;Shibuya, Yukina;Daikoku, Tohru
糖皮质激素和神经细胞凋亡诱导的活性氧（ROS）的产生之间的关系的功能的理解可能会导致一个新的策略，用于治疗或预防抑郁症。以往的研究表明，类黄酮类化合物，可能是一个有效的候选人对抑郁症相关的神经细胞凋亡所造成的氧化应激，然而，对受损的皮质酮（CORT）处理的神经细胞的保护作用的Butein尚未阐明。在本研究中，我们研究了在小鼠神经母细胞瘤Neuro 2A（N2 A）细胞分化过程中，Butein对CORT诱导的细胞毒性和神经突生长的保护作用。此外，证实了高浓度的Butein对培养细胞的影响。我们的研究结果表明，CORT治疗显着降低细胞活力，诱导细胞死亡。CORT通过线粒体功能障碍和caspase-3激活诱导细胞凋亡;这种细胞凋亡可能归因于ROS产生的DNA损伤，在本研究中发现用Butein预处理可显著抑制。我们发现，CORT产生显着的生长抑制视黄酸诱导的神经突起生长在N2 A细胞;然而，Butein显着增加神经突起的长度和诱导剂量依赖性细胞凋亡的细胞毒性在N2 A细胞。这项研究表明，低浓度的Butein可以防止CORT诱导的N2 A细胞的细胞毒性，并提供了初步的结果支持Butein在神经保护中的一些有益作用。
A functional understanding of the relationship between glucocorticoids and neuronal apoptosis induced by the production of reactive oxygen species (ROS) may lead to a novel strategy for the treatment or prevention of depression. Previous reports suggest that butein, a type of flavonoids, may be a potent candidate against depression-related neuronal cell apoptosis caused by oxidative stress; however, the protective effects of butein on damaged corticosterone (CORT)-treated neuronal cells has not been elucidated. In the present study, we examined the protective effect of butein on CORT-induced cytotoxicity and neurite growth during cell differentiation of mouse neuroblastoma Neuro2A (N2A) cells. Moreover, the effect on cultured cells by high concentrations of butein was confirmed. Our results demonstrate that CORT treatment significantly decreases cell viability and induces cell death. CORT was suggested to induce apoptosis via mitochondrial dysfunction and caspase-3 activation; this apoptosis may be attributed to DNA damage by ROS generation, found in this study to be significantly inhibited by pretreatment with butein. We found that CORT produced significant growth suppression of retinoic acid-induced neurite outgrowth in N2A cells; however, butein significantly increased neurite length and induced dose-dependent apoptotic cytotoxicity in N2A cells. This study suggests that low concentration of butein can prevent CORT-induced cytotoxicity in N2A cells, and provides preliminary results supporting some of the beneficial roles of butein in neuroprotection.