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EP3, Prostaglandin E2 Receptor Subtype 3, Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage

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Abstract

EP3 is prostaglandin E2 receptor subtype 3 and mediates the activation of several signaling pathways, changing in cAMP levels, calcium mobilization, and activation of phospholipase C. Previous studies demonstrated a direct role for EP3 in various neurodegenerative disorders, such as stroke and Alzheimer disease. However, the distribution and function of EP3 in ICH diseases remain unknown. Here, we demonstrate that EP3 may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). From the results of Western blot and immunohistochemistry, we obtained a significant up-regulation of EP3 in neurons adjacent to the hematoma following ICH. Up-regulation of EP3 was found to be accompanied by the increased expression of active caspase-3 and pro-apoptotic Bcl-2-associated X protein (Bax) and decreased expression of anti-apoptotic protein B cell lymphoma-2 (Bcl-2) in vivo and vitro studies. Furthermore, the expression of these three proteins reduced active caspase-3 and Bax expression, while increased Bcl-2 were changed after knocking down EP3 by RNA interference in PC12 cells, further confirmed that EP3 might exert its pro-apoptotic function on neuronal apoptosis. Thus, EP3 may play a role in promoting the neuronal apoptosis following ICH.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (Nos. 81471188, 81371299). The work was also supported by Technology Innovation Programme of Nantong University (YKS14016).

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    Authors and Affiliations

    1. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Haidan Ni, Jiabing Shen, Yan Song, Maohong Cao, Xiaorong Liu, Jie Huang, Weidong Zhang, Lili Xie, Xiaojin Ning & Kaifu Ke

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    1. Haidan Ni
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    2. Jiabing Shen
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    3. Yan Song
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    Correspondence to Kaifu Ke.

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    Haidan Ni and Jiabing Shen contributed equally to this work.

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    Ni, H., Shen, J., Song, Y. et al. EP3, Prostaglandin E2 Receptor Subtype 3, Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage. Cell Mol Neurobiol 36, 971–980 (2016). https://doi.org/10.1007/s10571-015-0287-2

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