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γ-氨基丁酸、司来吉兰和奥氮平影响IMR-32细胞中参与γ-氨基丁酸能神经传递的基因表达。

GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.

作者信息

Filatova Elena, Kasian Anastasiya, Kolomin Timur, Rybalkina Ekaterina, Alieva Anelya, Andreeva Lyudmila, Limborska Svetlana, Myasoedov Nikolay, Pavlova Galina, Slominsky Petr, Shadrina Maria

机构信息

Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.

Laboratory of Tumor Cells Genetics, Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation Moscow, Russia.

出版信息

Front Pharmacol. 2017 Feb 28;8:89. doi: 10.3389/fphar.2017.00089. eCollection 2017.

DOI:10.3389/fphar.2017.00089
PMID:28293190
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5328971/
Abstract

Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method. As test substances, in addition to Selank, we selected the major GABA receptor ligand, GABA, the atypical antipsychotic, olanzapine, and combinations of these compounds (Selank and GABA; Selank and olanzapine). We found no changes in the mRNA levels of the genes studied under the effect of Selank. The combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA. When Selank was used in conjunction with olanzapine, the expression alterations of more genes were observed compared with olanzapine alone. The data obtained indicate that Selank has no direct effect on the mRNA levels of the GABAergic system genes in neuroblastoma IMR-32 cells. At the same time, our results partially confirm the hypothesis that the peptide may affect the interaction of GABA with GABA receptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied.

摘要

临床研究表明,塞尔ank具有与经典苯二氮卓类药物相当的抗焦虑作用,后者可通过变构调节GABA受体来增强GABA的抑制作用。这些数据表明,塞尔ank作用的分子机制可能也与其影响GABA能系统功能的能力有关。为了验证这一假设,我们使用qPCR方法研究了神经母细胞瘤IMR-32细胞培养物中84个参与GABA能系统功能和神经传递过程的基因的表达变化。作为测试物质,除了塞尔ank,我们还选择了主要的GABA受体配体GABA、非典型抗精神病药物奥氮平以及这些化合物的组合(塞尔ank和GABA;塞尔ank和奥氮平)。我们发现在塞尔ank作用下,所研究基因的mRNA水平没有变化。GABA和塞尔ank的联合作用导致在GABA作用下mRNA水平发生变化的基因表达变化几乎完全受到抑制。当塞尔ank与奥氮平联合使用时,与单独使用奥氮平相比,观察到更多基因的表达改变。获得的数据表明,塞尔ank对神经母细胞瘤IMR-32细胞中GABA能系统基因的mRNA水平没有直接影响。同时,我们的结果部分证实了该肽可能影响GABA与GABA受体相互作用的假设。我们的数据还表明,塞尔ank可能增强奥氮平对所研究基因表达的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/ae302ab4bdf8/fphar-08-00089-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/d225a1816107/fphar-08-00089-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/e892d7e72c03/fphar-08-00089-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/ae302ab4bdf8/fphar-08-00089-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/d225a1816107/fphar-08-00089-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/e892d7e72c03/fphar-08-00089-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c623/5328971/ae302ab4bdf8/fphar-08-00089-g0003.jpg

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本文引用的文献

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Front Pharmacol. 2016 Feb 18;7:31. doi: 10.3389/fphar.2016.00031. eCollection 2016.
2
The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action.Selank 类似物作用下炎症相关基因表达的暂时动态。
Mol Immunol. 2014 Mar;58(1):50-5. doi: 10.1016/j.molimm.2013.11.002. Epub 2013 Nov 27.
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Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes.
基于梯度提升决策树的靶基因与药物相互作用预测方法
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2-Iminobiotin Superimposed on Hypothermia Protects Human Neuronal Cells from Hypoxia-Induced Cell Damage: An Study.2-亚氨基生物素叠加低温保护人神经元细胞免受缺氧诱导的细胞损伤:一项研究。
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超越经典苯二氮䓬类药物:GABAA 受体亚型的新治疗潜力。
Nat Rev Drug Discov. 2011 Jul 29;10(9):685-97. doi: 10.1038/nrd3502.
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Regul Pept. 2011 Oct 10;170(1-3):18-23. doi: 10.1016/j.regpep.2011.05.001. Epub 2011 May 24.
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Functional characterization and high-throughput screening of positive allosteric modulators of α7 nicotinic acetylcholine receptors in IMR-32 neuroblastoma cells.IMR-32神经母细胞瘤细胞中α7烟碱型乙酰胆碱受体正变构调节剂的功能表征及高通量筛选
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