GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions
| Autor: | Hui-Ling Tang, Shu-Jing Liu, Mei-Mei Gao, Qi-Hua Zhao, Yue-Sheng Long, Ping Lu, Tao Zeng, Yong-Hong Chen, Yong-Hong Yi, Guo-Wang Lin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Untranslated region Male medicine.medical_treatment Sodium Channels 03 medical and health sciences Cellular and Molecular Neuroscience SCN3A Epilepsy Mice stomatognathic system Downregulation and upregulation Seizures Cell Line Tumor Gene expression medicine NAV1.3 Voltage-Gated Sodium Channel Animals Humans RNA Processing Post-Transcriptional Glyceraldehyde 3-phosphate dehydrogenase Pharmacology biology Sodium channel Glyceraldehyde-3-Phosphate Dehydrogenases medicine.disease Cell biology NAV1.1 Voltage-Gated Sodium Channel 030104 developmental biology HEK293 Cells Biochemistry biology.protein Diet Ketogenic Ketogenic diet Protein Binding |
| Zdroj: | Neuropharmacology. 113 |
| ISSN: | 1873-7064 |
| Popis: | Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions. We show that GAPDH binds to a conserved region in the 3' UTRs of human and mouse SCN1A and SCN3A genes, which decreases and increases genes' expressions by affecting mRNA stability through SCN1A 3' UTR and SCN3A 3' UTR, respectively. In seizure mice, the upregulation and phosphorylation of GAPDH enhance its binding to the 3' UTR, which lead to downregulation of Scn1a and upregulation of Scn3a. Furthermore, administration of KD generates β-hydroxybutyric acid which rescues the abnormal expressions of Scn1a and Scn3a by weakening the GAPDH's binding to the element. Taken together, these data suggest that GAPDH-mediated expression regulation of sodium channel genes may be associated with epilepsy and the anticonvulsant action of KD. |
| Databáze: | OpenAIRE |
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