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硝普钠通过p38信号通路对分化神经干细胞存活的抑制作用

The Inhibition Effects of Sodium Nitroprusside on the Survival of Differentiated Neural Stem Cells through the p38 Pathway.

作者信息

Jiao Lingling, Xu Tongying, Du Xixun, Chen Xi, Jiao Qian, Jiang Hong

机构信息

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, School of Basic Medicine, Qingdao University, Qingdao 266071, China.

College of Health and Life Science, University of Health and Rehabilitation Sciences, Qingdao 266071, China.

出版信息

Brain Sci. 2023 Mar 3;13(3):438. doi: 10.3390/brainsci13030438.

Abstract

Nitric oxide (NO) is a crucial factor in regulating neuronal development. However, certain effects of NO are complex under different physiological conditions. In this study, we used differentiated neural stem cells (NSCs), which contained neural progenitor cells, neurons, astrocytes, and oligodendrocytes, to observe the physiological effects of sodium nitroprusside (SNP) on the early developmental stage of the nervous system. After SNP treatment for 24 h, the results showed that SNP at 100 μM, 200 μM, 300 μM, and 400 μM concentrations resulted in reduced cell viability and increased cleaved caspase 3 levels, while no significant changes were found at 50 μM. There were no effects on neuronal differentiation in the SNP-treated groups. The phosphorylation of p38 was also significantly upregulated with SNP concentrations of 100 μM, 200 μM, 300 μM, and 400 μM, with no changes for 50 μM concentration in comparison with the control. We also observed that the levels of phosphorylation increased with the increasing concentration of SNP. To further explore the possible role of p38 in SNP-regulated survival of differentiated NSCs, SB202190, the antagonist of p38 mitogen-activated protein kinase, at a concentration of 10 mM, was pretreated for 30 min, and the ratio of phosphorylated p38 was found to be decreased after treatment with SNP. Survival and cell viability increased in the SB202190 and SNP co-treated group. Taken together, our results suggested that p38 is involved in the cell survival of NSCs, regulated by NO.

摘要

一氧化氮(NO)是调节神经元发育的关键因素。然而,在不同生理条件下,NO的某些作用较为复杂。在本研究中,我们使用了包含神经祖细胞、神经元、星形胶质细胞和少突胶质细胞的分化神经干细胞(NSC),以观察硝普钠(SNP)对神经系统早期发育阶段的生理影响。SNP处理24小时后,结果显示,浓度为100μM、200μM、300μM和400μM的SNP导致细胞活力降低和裂解的半胱天冬酶3水平升高,而50μM时未发现显著变化。SNP处理组对神经元分化没有影响。100μM、200μM、300μM和400μM浓度的SNP也显著上调了p38的磷酸化水平,与对照组相比,50μM浓度时没有变化。我们还观察到磷酸化水平随SNP浓度的增加而升高。为了进一步探讨p38在SNP调节分化NSC存活中的可能作用,以10 mM的浓度预处理p38丝裂原活化蛋白激酶拮抗剂SB202190 30分钟,发现用SNP处理后磷酸化p38的比例降低。SB202190和SNP共同处理组的细胞存活率和活力增加。综上所述,我们的结果表明p38参与了由NO调节的NSC细胞存活过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9476/10046126/7efd5dd4b9c4/brainsci-13-00438-g001.jpg

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