Resveratrol potentiates intracellular ascorbic acid enrichment through dehydroascorbic acid transport and/or its intracellular reduction in HaCaT cells.

L-Ascorbic acid (AsA), a reduced vitamin C (VC), is an important antioxidant, and the internal accumulation and maintenance of AsA are thought to play a significant role in various physiological activities in humans. We focused on resveratrol (RSV), a natural polyphenolic compound, as a candidate for an AsA transport modulator and investigated whether RSV can affect the intracellular VC accumulation after either AsA or dehydroascorbic acid (DHA) addition in HaCaT keratinocytes. Our results demonstrate that RSV treatment could significantly enhance intracellular VC levels after either AsA or DHA supplementation, and intracellular VC accumulated mainly as AsA. Our results also indicate that most of the intracellular transported DHA was reduced to AsA and accumulated after uptake into cells. In addition, RSV could induce several AsA or DHA transport-related and intracellular DHA reduction-related genes including SVCT2, GLUT3, TXNRD2, and TXNRD3, necessary for AsA transport, DHA transport, and DHA reduction/regeneration, respectively. On the other hand, the both protein expression levels and the localizations of sodium-dependent vitamin C transporters 2 (SVCT2) and glucose transporter 3(GLUT3) were scarcely affected by RSV treatment. Furthermore, RSV-induced enrichment of intracellular AsA levels was completely suppressed by a GLUT inhibitor cytochalasin B. These results suggest that RSV can potentiate intracellular AsA accumulation via activation of the DHA transport and subsequent intracellular reduction from DHA to AsA. Thus, RSV might be useful for maintaining substantial AsA accumulation in the skin keratinocytes.