Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells.
Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells.
复制标题
DOI：
10.1007/s12640-015-9534-z
复制
发表时间：
2015-08
影响因子：
3.7
通讯作者：
Zhu, Meng-Yang
中科院分区：
文献类型：
--
作者：
Wang, Yan;Hilton, Benjamin A.;Cui, Kui;Zhu, Meng-Yang
DNA损伤是细胞应激和损伤的一种形式。增加的系统性DNA损伤与神经退行性疾病的致病性发展有关。抑郁症发生在相对较高比例的退行性疾病患者中，抗抑郁药通常用于缓解抑郁症状。然而，很少有研究试图阐明为什么不同类型的抗抑郁药在缓解抑郁症症状方面具有相似的效果。以前，我们证明神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺（DSP 4）-和喜树碱（CPT）-诱导的DNA损伤反应在SH-SY 5 Y细胞，DSP 4引起细胞周期阻滞，主要是在S期。本研究表明，CPT治疗也导致类似的细胞周期停滞。一些经典的抗抑郁药物可以减轻DSP 4或CPT诱导的SH-SY 5 Y细胞DNA损伤反应。细胞活力检测表明，DSP 4和CPT均引起细胞死亡，自发给予一些测试的抗抑郁药可以防止细胞死亡。流式细胞术分析表明，大多数测试的抗抑郁药保护细胞免于被逮捕在S期。这些结果表明，阻断DNA损伤反应可能是抗抑郁药的一个重要药理学特征。探索潜在的机制可能有助于改善退行性疾病和精神疾病中出现的抑郁症的治疗策略。
DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT)-induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases.
登录
查看更多内容
影响因子：
3.4
作者：
Cheung, Yuen-Ting;Lau, Way Kwok-Wai;Chang, Raymond Chuen-Chung
通讯作者：
Chang, Raymond Chuen-Chung
影响因子：
4.2
作者：
Choi, HJ;Lee, SY;Hwang, OY
通讯作者：
Hwang, OY
影响因子：
3.3
作者：
Brummelte, S.;Galea, L. A. M.
通讯作者：
Galea, L. A. M.
影响因子：
7.3
作者：
Chiou, Shih-Hwa;Ku, Hung-Hai;Chang, Yuh-Lih
通讯作者：
Chang, Yuh-Lih
影响因子：
5
作者：
DOOLEY, DJ;HEAL, DJ;GOODWIN, GM
通讯作者：
GOODWIN, GM