Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway
| Autor: | Ye-Hui Liu, Qin-De Qi, Yan-Hui Zhang, Ai-Qin Qi, Jun-Ling Zhu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Kainic acid Down-Regulation Apoptosis Hippocampal formation Pharmacology MAP Kinase Kinase Kinase 5 Hippocampus Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Seizures Heat shock protein medicine Cyclic AMP Animals ASK1 HSP20 Heat-Shock Proteins Phosphorylation Inflammation Neurons Kainic Acid Base Sequence Kinase Cell Biology General Medicine Cyclic AMP-Dependent Protein Kinases 030104 developmental biology chemistry Epileptic seizure medicine.symptom 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cellular and molecular neurobiology. 39(1) |
| ISSN: | 1573-6830 |
| Popis: | Epilepsy is a commonly occurring neurological disease that has a large impact on the patient's daily life. Phosphorylation of heat shock protein B6 (HspB6) has been reported to protect the central nervous system. In this investigation, we explored whether HspB6 played a positive effect on epilepsy with the involvement of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway. The epileptic seizure was induced in rats by intraperitoneal injection of kainic acid (KA). The extent of HspB6 phosphorylation and expressions of HspB6, PKA, and inflammatory factors TNF-α, IL-1β, and IL-6 were quantified along with neuronal apoptosis. To further understand the regulatory mechanism of the HspB6 in the hippocampus, we altered the expression and the extent of HspB6 phosphorylation to see whether the cAMP-PKA pathway was inactivated or not in hippocampal neurons of rats post KA. Results showed that HspB6 was poorly expressed, resulting in the inactivation of the cAMP-PKA pathway in rats post KA, as well as an aggravated inflammatory response and hippocampal neuronal apoptosis. HspB6 overexpression and the cAMP-PKA pathway activation decreased the expression of inflammatory factors and inhibited hippocampal neuronal apoptosis. Additionally, HspB6 phosphorylation further augments the inhibitory effects of HspB6 on the inflammatory response and hippocampal neuronal apoptosis. The cAMP-PKA pathway activation was found to result in increased HspB6 phosphorylation. HspB6 decreased apoptosis signal-regulating kinase 1 (ASK1) expression to inhibit inflammatory response and hippocampal neuronal apoptosis. Collectively, our findings demonstrate that activation of the cAMP-PKA pathway induces overexpression and partial phosphorylation of HspB6 lead to the inhibition of ASK1 expression. This in turn protects rats against epilepsy and provides a potential approach to prevent the onset of epileptic seizure in a clinical setting. |
| Databáze: | OpenAIRE |
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