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Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway

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Abstract

In addition to its original application for treating tuberculosis, rifampicin has multiple potential neuroprotective effects in chronic neurodegenerative diseases including Parkinson’s disease (PD) and Alzheimer’s disease. Inflammatory reactions and the PI3K/Akt pathway are strongly implicated in dopaminergic neuronal death in PD. This study aims to investigate whether rifampicin protects rotenone-lesioned SH-SY5Y cells via regulating PI3K/Akt/GSK-3β/CREB pathway. Rotenone-treated SH-SY5Y cells were used as the cell model to investigate the neuroprotective effects of rifampicin. Cell viability and apoptosis of SH-SY5Y cells were determined by CCK-8 assay and flow cytometry, respectively. The expression of Akt, p-Akt, GSK-3β, p-GSK-3β, CREB and p-CREB were measured by Western blot. Our results showed that the cell viability and level of phospho-CREB significantly decreased in SH-SY5Y cells exposed to rotenone when compared to the control group. Both the cell viability and the expression of phospho-CREB in cells pretreated with rifampicin were higher than those of cells exposed to rotenone alone. Moreover, pretreatment of SH-SY5Y cells with rifampicin enhanced phosphorylation of Akt and suppressed activity of GSK-3β. The addition of LY294002, a PI3K inhibitor, could suppress phosphorylation of Akt and CREB and activate GSK-3β, resulting in abolishment of neuroprotective effects of rifampicin on cells exposed to rotenone. Rifampicin provides neuroprotection against dopaminergic degeneration, partially via the PI3K/Akt/GSK-3β/CREB signaling pathway. These findings suggest that rifampicin could be an effective and promising neuroprotective candidate for treating PD.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Grant Numbers 81571244, 81771378, 81371391 and 81503052), the Public Welfare Research and Capacity Building Project of Guangdong Province (Grant Number 2014A020212164), the Natural Science Foundation of Guangdong Province (Grant Numbers 2014A030313202, 2016A030313322 and 2017A030313840), the Guangzhou Science and Technology Research Project (Grant Number 201607010219), and the Fundamental Research Fund for University Youth Scholars (Grant Number 17ykpy39).

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Author notes

  1. Xia Wu, Yanran Liang and Xiuna Jing have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510080, Guangdong, China

    Xia Wu, Yanran Liang, Xiuna Jing, Danyu Lin, Ying Chen, Sudan Peng, Dezhi Zheng, Zhifen Zeng, Ming Lei, Kaixun Huang & Enxiang Tao

  2. Department of Neurology, Shenzhen Nanshan District Xili People’s Hospital, No. 2051 Xili Liuxian Avenue, Shenzhen, 518055, China

    Xia Wu

  3. Department of Emergency, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510080, China

    Tianen Zhou

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Wu, X., Liang, Y., Jing, X. et al. Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway. Neurochem Res 43, 886–893 (2018). https://doi.org/10.1007/s11064-018-2494-y

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