The Role of EZH2 Inhibitor, GSK-126, in Seizure Susceptibility
| العنوان: | The Role of EZH2 Inhibitor, GSK-126, in Seizure Susceptibility |
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| المؤلفون: | Yaxin Su, Zhongcheng Wang, Ting Lan, Dezheng Zhuang |
| المصدر: | Journal of Molecular Neuroscience. 71:556-564 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Indoles, Pyridones, Hippocampus, Antineoplastic Agents, macromolecular substances, Pharmacology, Biology, Histones, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Seizures, Animals, Gene silencing, Enhancer of Zeste Homolog 2 Protein, Neurochemistry, Enzyme Inhibitors, Enhancer, Gene, Mice, Inbred BALB C, EZH2, General Medicine, 030104 developmental biology, Histone, Histone methyltransferase, biology.protein, 030217 neurology & neurosurgery |
| الوصف: | GSK-126 is recognized as an inhibitor of enhancer of zeste homolog-2 (EZH2) activity. Because of its inhibition of EZH2 activation, GSK-126 is considered a potential anti-tumor drug. EZH2 is a histone methyltransferase that catalyzes histone 3 tri-methylation at lysine 27 (H3K27me3), resulting in gene silencing. A previous report showed that decreased H3K27me3 levels in the hippocampus may promote seizure susceptibility, possibly restricting the clinical application of GSK-126. The role of GSK-126 in seizure susceptibility was investigated in this study. We first determined a critical concentration of pentamethazol (PTZ) under which mice exhibit no seizures. We then found that mice pretreated with GSK-126 and injected with the same concentration of PTZ experienced marked convulsions. Peripheral injections of GSK-126 decreased H3K27me3 levels in the hippocampus of mice, while some seizure-related genes (Oasl1, Sox7, armcx5, Ncx3, etc.) were found to be differentially expressed in the hippocampus of those mice . These differences in the expression levels might reflect the crucial role of these genes and related pathways in the promotion of seizure susceptibility. Our results suggest that GSK-126 promotes seizure susceptibility due to its role as an EZH2 inhibitor. These findings may provide evidence to support the development of GSK-126 as a clinical drug. |
| تدمد: | 1559-1166 0895-8696 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e05b47895148e51e502648fc6d52641Test https://doi.org/10.1007/s12031-020-01677-7Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....6e05b47895148e51e502648fc6d52641 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591166 08958696 |
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