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Updated: Aug 29, 2025

A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
Published on: April 11, 2014
Valproic acid upregulates sodium-dependent vitamin C transporter-2 functional expression in neuronal cells
Trevor Teafatiller1, Sreya Subramanian1, Felerico E Marquez1
1Department of Medicine, University of California, Irvine, CA 92697, United States of America.
Abstract:
Neuronal uptake of ascorbic acid (AA) in humans occurs via the human sodium-dependent vitamin C transporter-2 (hSVCT2). Recent studies show that a significantly lower level of vitamin C is present in the blood of epileptic patients. Consequently, focused studies investigating the involved molecular mechanisms for hSVCT2 regulation are vital to enhance vitamin C body homeostasis. Currently, little is known about the role of valproic acid (VPA), a drug utilized to treat epilepsy and a class I histone deacetylase inhibitor (HDACi), on AA uptake in neuronal systems. Thus, this study aims to examine the effect of VPA on hSVCT2 functional expression in neuronal cells. VPA treatment upregulated the AA uptake and this increased AA uptake was associated with a significant increase in hSVCT2 expression and SLC23A2 promoter activity in SH-SY5Y cells. Knockdown of HDAC2, a predominant isoform in neuronal systems, significantly increased hSVCT2 functional expression. VPA treatment in mice displayed increased mouse (m)SVCT2 protein, mRNA and heterogenous nuclear RNA (hnRNA) expression in the brain. In addition, Yin Yang-1 (YY1), a transcription factor that drives the SLC23A2 promoter activity, protein and mRNA expression levels were markedly upregulated in VPA-treated SH-SY5Y cells and mice brain. Together, our findings suggest that VPA upregulates the functional expression of SVCT2 via HDAC2 and transcriptional mechanism(s).
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