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miR-128 在癫痫中上调,并通过 SIRT1 级联促进细胞凋亡。

miR‑128 is upregulated in epilepsy and promotes apoptosis through the SIRT1 cascade.

机构信息

Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.

Department of Neurology, Taishan Medical University, Taian, Shandong 271016, P.R. China.

出版信息

Int J Mol Med. 2019 Aug;44(2):694-704. doi: 10.3892/ijmm.2019.4223. Epub 2019 May 30.

Abstract

The present study aimed to examine the functional and molecular effects of miR‑128 in epilepsy, in order to investigate its potential protective mechanisms. Firstly, miR‑128 expression in rats with lithium chloride‑induced epilepsy was demonstrated to be increased compared with the control rats. Subsequently, results from an in vitro epilepsy model demonstrated that overexpression of miR‑128 promoted nerve cell apoptosis, increased the protein expression of tumor protein p53, BCL2 associated X (Bax) and Cytochrome c, and enhanced caspase‑3/9 activity, whereas it suppressed the protein expression of sirtuin 1 (SIRT1). In addition, these alterations may be reversed by the downregulation of miR‑128. Furthermore, treatment with CAY10602, a SIRT1 agonist, reduced the effects of miR‑128 on nerve cells in vitro. Treatment with pifithrin‑β hydrobromide, a p53 inhibitor, was additionally able to mitigate the effects of miR‑128 in vitro. In conclusion, the present findings indicated that anti‑miR‑128 may exert neuroprotective effects in epilepsy, through the SIRT1/p53/Bax/Cytochrome c/caspase signaling pathway.

摘要

本研究旨在探讨 miR-128 在癫痫中的功能和分子作用,以研究其潜在的保护机制。首先,与对照组大鼠相比,氯化锂诱导癫痫大鼠的 miR-128 表达增加。随后,体外癫痫模型的结果表明,miR-128 的过表达促进神经细胞凋亡,增加肿瘤蛋白 p53、B 细胞淋巴瘤-2 相关 X(Bax)和细胞色素 c 的蛋白表达,并增强半胱氨酸天冬氨酸蛋白酶-3/9 活性,而抑制沉默调节蛋白 1(SIRT1)的蛋白表达。此外,这些改变可能通过下调 miR-128 而逆转。此外,SIRT1 激动剂 CAY10602 的处理减少了 miR-128 在体外对神经细胞的作用。p53 抑制剂 pifithrin-β 氢溴酸盐的处理还能够减轻 miR-128 在体外的作用。综上所述,这些发现表明,抗 miR-128 可能通过 SIRT1/p53/Bax/Cytochrome c/caspase 信号通路在癫痫中发挥神经保护作用。

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