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

  • Jakkapong Muangsab
  • Peerada Prommeenate
  • Banthit Chetsawang
  • Pennapa Chonpathompikunlert
  • Wanida Sukketsiri
  • Pilaiwanwadee Hutamekalin
Keywords: Valproic acid, Neuronal cells, Cyclin-dependent kinase 5, p35, Erk signaling pathway

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 concentrationdependent 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.

Published
2021-07-07
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996