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Protective Effect of DHT on Apoptosis Induced by U18666A via PI3K/Akt Signaling Pathway in C6 Glial Cell Lines

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Abstract

Various useful animal models, such as Alzheimer’s disease and Niemann–Pick disease, were provided by U18666A. However, the pathogenesis of U18666A-induced diseases, including U18666A-mediated apoptosis, remains incompletely elucidated, and therapeutic strategies are still limited. Dihydrotestosterone (DHT) has been reported to contribute to the prevention and treatment of neurodegenerative disorders. Our study investigated the neuroprotective activity of DHT in U18666A-related diseases. Apoptosis of C6 cells was detected by Hoechst 33258 fluorescent staining and flow cytometry with annexin V-FITC/PI dual staining. Cell viability was assessed using Cell Counting Kit-8. Expression of apoptosis-related proteins, such as Akt, seladin-1, Bcl-2 family proteins, and caspase-3, was determined using Western blot. Our results demonstrated that the apoptotic rate of C6 cells significantly increased after U18666A addition, but was remarkably reduced after DHT treatment. Pretreatment with DHT attenuated U18666A-induced cell viability loss. PI3K inhibitor LY294002 could suppress DHT anti-apoptotic effect. Furthermore, we discovered that U18666A could significantly downregulate seladin-1 expression in a dose-dependent manner, but no significant change was observed in Bcl-xL, Bax, and P-Akt protein expressions. Compared with U18666A-treated group, the expression of P-Akt, seladin-1, and Bcl-xL significantly increased, and the expression of Bax and caspase-3 remarkably reduced after DHT treatment. However, in the presence of LY294002, the effect of DHT was reversed. In conclusion, we found that seladin-1 may take part in U18666A-induced apoptosis. DHT may inhibit U18666A-induced apoptosis by regulating downstream apoptosis-related proteins including seladin-1, caspase-3, Bcl-xL, and Bax through activation of the PI3K/Akt signal pathway.

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Authors and Affiliations

  1. Department of Neurology, Jinshan Hospital Affiliated to Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai, 201508, China

    Kai Yao, Junfeng Wu, Jianfeng Zhang, Jimei Bo, Zhen Hong & Hengbing Zu

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  1. Kai Yao
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  2. Junfeng Wu
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  3. Jianfeng Zhang
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  5. Zhen Hong
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  6. Hengbing Zu
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Correspondence to Hengbing Zu.

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Yao, K., Wu, J., Zhang, J. et al. Protective Effect of DHT on Apoptosis Induced by U18666A via PI3K/Akt Signaling Pathway in C6 Glial Cell Lines. Cell Mol Neurobiol 36, 801–809 (2016). https://doi.org/10.1007/s10571-015-0263-x

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