Valproic acid upregulates the expression of the p75NTR/sortilin receptor complex to induce neuronal apoptosis.

ABSTRACT: The antiepileptic and mood stabilizer agent valproic acid (VPA) has been shown to exert anti-tumour effects and to cause neuronal damage in the developing brain through mechanisms not completely understood. In the present study we show that prolonged exposure of SH-SY5Y and LAN-1 human neuroblastoma cells to clinically relevant concentrations of VPA caused a marked induction of the protein and transcript levels of the common neurotrophin receptor p75NTR and its co-receptor sortilin, two promoters of apoptotic cell death in response to proneurotrophins. VPA induction of p75NTR and sortilin was associated with an increase in plasma membrane expression of the receptor proteins and was mimicked by cell treatment with several histone deacetylase (HDAC) inhibitors. VPA and HDAC1 knockdown decrea

SUBMITTER: Dedoni S 

PROVIDER: S-EPMC7527367 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature