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GPR30 Activation Contributes to the Puerarin-Mediated Neuroprotection in MPP+-Induced SH-SY5Y Cell Death

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Abstract

The neuroprotective action of puerarin in Parkinson’s disease (PD) models has been well investigated. However, the mechanisms involved in protection have not been completely understood. G protein-coupled receptor 30 (GPR30) is a G protein-coupled estrogen receptor and considered a potential target in the neuroprotection against PD. In this study, we investigated whether puerarin prevented against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death via GPR30. Our results showed that the GPR30 agonist, G1, exhibited puerarin-mediated neuroprotection against MPP+-induced cell death of SH-SY5Y cells. This protective action was reversed by the GPR30 antagonist. Moreover, a time- and concentration-dependent effect of puerarin on GPR30 expression was verified at the protein level but not at the mRNA level. Further, we showed that an mTor-dependent new GPR30 synthesis contributed to the protection conferred by puerarin. Finally, glial cell line-derived neurotrophic factor (GDNF) levels were enhanced by puerarin and G1 in both control and MPP+-lesioned cells via GPR30. Taken together, our data strongly suggest that puerarin prevents MPP+-induced cell death via facilitating GPR30 expression and GDNF release.

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Acknowledgments

This work was supported by Natural Science Foundation of Hebei Province, China (Grant No. H2014209300), and Research Project of Administration of Traditional Chinese Medicine of Hebei Province, China (Grant No. 2013180), to YC. This work was also supported by the National Natural Science Foundation of China (81673716, 81601181) to GZ.

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Authors and Affiliations

  1. Jitang College of North China University of Science and Technology, Tangshan, 063000, China

    Yue-Fa Cheng, Yue-Sheng Xie, Yan Jiang, Lan Guo, Ya-Li Guan, Ying-Shuo Liu & Jun Zhang

  2. Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China

    Guoqi Zhu

  3. College of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, 063000, China

    Qing-Wen Wu

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  1. Yue-Fa Cheng
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Correspondence to Yue-Fa Cheng.

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Yue-Fa Cheng and Guoqi Zhu contributed equally to this work.

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Cheng, YF., Zhu, G., Wu, QW. et al. GPR30 Activation Contributes to the Puerarin-Mediated Neuroprotection in MPP+-Induced SH-SY5Y Cell Death. J Mol Neurosci 61, 227–234 (2017). https://doi.org/10.1007/s12031-016-0856-y

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