Indirubin derivatives protect against endoplasmic reticulum stress-induced cytotoxicity and down-regulate CHOP levels in HT22 cells.
Indirubin derivatives protect against endoplasmic reticulum stress-induced cytotoxicity and down-regulate CHOP levels in HT22 cells.
复制标题
靛玉红衍生物可防止内质网应激诱导的细胞毒性，并下调 HT22 细胞中的 CHOP 水平。
DOI：
10.1016/j.bmcl.2017.10.069
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ito Y.
中科院分区：
文献类型：
--
作者：
Kosuge Y;Saito H;Haraguchi T;Ichimaru Y;Ohashi S;Miyagishi H;Kobayashi S;Ishige K;Miyairi S;Ito Y.
靛玉红及其衍生物已被报道显示出抗癌和抗炎活性。最近，其衍生的一些类似物已被证明具有神经保护潜力。内质网（ER）应激已被证明有助于各种神经退行性疾病的发病机制，而靛玉红衍生物对ER应激诱导的细胞死亡的影响尚未得到解决。在本研究中，一系列的44靛玉红衍生物的制备，寻找一种新的神经保护剂对ER应激诱导的神经元死亡。MTT还原实验表明，内质网应激诱导剂衣霉素（TM）可显著降低海马神经元HT 22细胞的存活率。在测试的化合物中，8个显示出对TM诱导的细胞死亡的显着抑制活性。蛋白质印迹分析表明，这些类似物的应用程序的细胞同时TM减少TM诱导的表达CHOP，一个既定的调解ER压力。我们的研究结果表明，这些靛玉红衍生物对ER应激诱导的神经元死亡的预防作用可能是由于，至少部分是由于衰减的CHOP依赖的信号系统。
Indirubin and its derivatives have been reported to exhibit anti-cancer and anti-inflammatory activities. Recently, some of its derived analogs have been shown to have neuroprotective potential. Endoplasmic reticulum (ER) stress has been demonstrated to contribute to the pathogenesis of various neurodegenerative diseases, whereas the effects of indirubin derivatives on ER stress-induced cell death have not been addressed. In the present study, a series of 44 derivatives of indirubin was prepared to search for a novel class of neuroprotective agents against ER stress-induced neuronal death. The MTT reduction assay indicated that tunicamycin (TM), an inducer of ER stress, significantly decreased the viability of hippocampal neuronal HT22 cells. Among the compounds tested, eight showed significant inhibitory activity against TM-induced cell death. Western blot analysis showed that application of these analogs to the cells simultaneously with TM reduced the TM-induced expression of CHOP, an established mediator of ER stress. Our results suggest that the preventive effect of these indirubin derivatives against ER stress-induced neuronal death may be due, at least in part, to attenuation of the CHOP-dependent signaling system.