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Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway

  • Ai-Qin Qi
  • Yan-Hui Zhang
  • Qin-De Qi
  • Ye-Hui Liu
  • Jun-Ling Zhu
Original Research
  • 27 Downloads

Abstract

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.

Keywords

Epilepsy Heat shock protein B6 cAMP-PKA signaling pathway Phosphorylation Inflammatory response Hippocampal neuronal apoptosis 

Notes

Acknowledgements

We would like to express our sincerest appreciation and gratitude to the reviewers for their helpful comments and insight on this article.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ai-Qin Qi
    • 1
  • Yan-Hui Zhang
    • 2
  • Qin-De Qi
    • 1
  • Ye-Hui Liu
    • 1
  • Jun-Ling Zhu
    • 1
  1. 1.Department of NeurologyLaiwu Hospital Affiliated to Taishan Medical UniversityLaiwuPeople’s Republic of China
  2. 2.Department of NeurologyBeijing Haidian HospitalBeijingPeople’s Republic of China

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