Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Jakkapong Muangsab¹, Peerada Prommeenate², Banthit Chetsawang³, Pennapa Chonpathompikunlert⁴, Wanida Sukketsiri⁵, Pilaiwanwadee Hutamekalin¹

¹Department of Physiology, Faculty of Science, Prince of Songkla University, Hat yai, Songkhla 90112; ²Biochemical Engineering and Pilot Plant Research and Development (BEC) Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, King Mongkut's University of Technology Thonburi, Bangkok 10150; ³Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom 73170; ⁴Expert Centre of Innovative Health Food (Innofood), Thailand Institute of Scientific and Technological Research (TISTR), Pathumthani 12120; ⁵Department of Pharmacology, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand.

For correspondence:- Pilaiwanwadee Hutamekalin Email: pilaiwanwadee.h@psu.ac.th Tel:+6674288207

Accepted: 23 October 2019 Published: 30 November 2019

Citation: Muangsab J, Prommeenate P, Chetsawang B, Chonpathompikunlert P, Sukketsiri W, Hutamekalin P. Protective effect of valproic acid on MPP+-induced neurotoxicity in dopaminergic SH-SY5Y cells through Cdk5/p35/Erk signaling cascade. Trop J Pharm Res 2019; 18(11):2255-2261 doi: 10.4314/tjpr.v18i11.4

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: Valproic acid, Neuronal cells, Cyclin-dependent kinase 5, p35, Erk signaling pathway