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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.
Cell Mol Neurobiol. 2019 Jan; 39(1):111-122.CM

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.

Authors+Show Affiliations

Department of Neurology, Laiwu Hospital Affiliated to Taishan Medical University, No. 001, Xuehu Street, Changshao North Road, Laicheng District, Laiwu, 271199, Shandong, People's Republic of China.Department of Neurology, Beijing Haidian Hospital, Beijing, 100080, People's Republic of China.Department of Neurology, Laiwu Hospital Affiliated to Taishan Medical University, No. 001, Xuehu Street, Changshao North Road, Laicheng District, Laiwu, 271199, Shandong, People's Republic of China.Department of Neurology, Laiwu Hospital Affiliated to Taishan Medical University, No. 001, Xuehu Street, Changshao North Road, Laicheng District, Laiwu, 271199, Shandong, People's Republic of China.Department of Neurology, Laiwu Hospital Affiliated to Taishan Medical University, No. 001, Xuehu Street, Changshao North Road, Laicheng District, Laiwu, 271199, Shandong, People's Republic of China. zhujl_lw@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30511325

Citation

Qi, Ai-Qin, et al. "Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats By Activating the cAMP-PKA Pathway." Cellular and Molecular Neurobiology, vol. 39, no. 1, 2019, pp. 111-122.
Qi AQ, Zhang YH, Qi QD, et al. Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway. Cell Mol Neurobiol. 2019;39(1):111-122.
Qi, A. Q., Zhang, Y. H., Qi, Q. D., Liu, Y. H., & Zhu, J. L. (2019). Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway. Cellular and Molecular Neurobiology, 39(1), 111-122. https://doi.org/10.1007/s10571-018-0637-y
Qi AQ, et al. Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats By Activating the cAMP-PKA Pathway. Cell Mol Neurobiol. 2019;39(1):111-122. PubMed PMID: 30511325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway. AU - Qi,Ai-Qin, AU - Zhang,Yan-Hui, AU - Qi,Qin-De, AU - Liu,Ye-Hui, AU - Zhu,Jun-Ling, Y1 - 2018/12/03/ PY - 2018/06/08/received PY - 2018/11/14/accepted PY - 2018/12/5/pubmed PY - 2019/4/9/medline PY - 2018/12/5/entrez KW - Epilepsy KW - Heat shock protein B6 KW - Hippocampal neuronal apoptosis KW - Inflammatory response KW - Phosphorylation KW - cAMP-PKA signaling pathway SP - 111 EP - 122 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 39 IS - 1 N2 - 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. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/30511325/Overexpressed_HspB6_Underlines_a_Novel_Inhibitory_Role_in_Kainic_Acid_Induced_Epileptic_Seizure_in_Rats_by_Activating_the_cAMP_PKA_Pathway_ L2 - https://doi.org/10.1007/s10571-018-0637-y DB - PRIME DP - Unbound Medicine ER -