Protective effect of valproic acid on MPP+-induced neurotoxicity in dopaminergic SH-SY5Y cells through Cdk5/p35/Erk signaling cascade

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PEERADA PROMMEENATE

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Publication Details

Author list: Muangsab J., Prommeenate P., Chetsawang B., Chonpathompikunlert P., Sukketsiri W., Hutamekalin P.

Publisher: University of Benin

Publication year: 2019

Volume number: 18

Issue number: 11

Start page: 2255

End page: 2261

Number of pages: 7

ISSN: 1596-5996

eISSN: 1596-5996

URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078036837&doi=10.4314%2ftjpr.v18i11.4&partnerID=40&md5=e57ee8d7214d6473e8447a40b30c833f

Languages: English-Great Britain (EN-GB)

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Abstract

Purpose: To investigate the neuroprotective effect of valproic acid (VPA) on 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic cell loss in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) generation in MPP+-treated SH-SY5Y cells was investigated by DCFH-DA. Apoptotic cell death was confirmed by Hoechst 33342 staining. The protective effect of VPA via Cdk5 and p35 cascade was investigated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot (WB) analysis. In addition, further investigation on cell survival was performed using Western blot analysis through Erk signaling pathway. Results: Cell viability was dramatically decreased in cells treated with MPP+ in a concentration-dependent manner (p < 0.05). Pre-treatment with VPA ameliorated MPP+-induced death of dopaminergic cell via inhibition of ROS generation (p < 0.05). VPA restored Cdk5 and p35 expression and significantly increased cell survival mediated by Erk activity (pErk/Erk). Conclusion: The results from this study confirmed that VPA attenuated MPP+-induced dopaminergic cell death by the inhibition of ROS production via Cdk5/p35 cascade and Erk signaling pathway. VPA is thus a potential therapeutic candidate for the treatment of dopaminergic cell death via Cdk5/p35 cascade. ฉ 2019 The authors. This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords

Cyclin-dependent kinase 5, Erk signaling pathway, Keyword: Valproic acid, Neuronal cells, P35