Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure

Am J Physiol Cell Physiol. 2016 Jul 1;311(1):C129-35. doi: 10.1152/ajpcell.00042.2016. Epub 2016 Apr 27.


Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PACs). PACs obtain AA from their surroundings via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PACs, but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters 1 and 2 [i.e., sodium-dependent vitamin C transporter-1 (SVCT-1) and SVCT-2] in mouse and human PACs and found SVCT-2 to be the predominant transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA, and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic alcohol effect on AA uptake by PACs. We also observed significant epigenetic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol-exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).

Keywords: acinar cells; epigenetics; pancreas; uptake; vitamin C.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Alcohol Drinking / metabolism
  • Animals
  • Ascorbic Acid / metabolism*
  • Biological Transport
  • Cell Line, Tumor
  • Down-Regulation
  • Epigenesis, Genetic
  • Ethanol / toxicity*
  • Humans
  • Mice
  • Models, Animal
  • Pancreas, Exocrine / drug effects*
  • Pancreas, Exocrine / metabolism
  • Pancreas, Exocrine / pathology
  • RNA, Heterogeneous Nuclear / genetics
  • RNA, Heterogeneous Nuclear / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sodium-Coupled Vitamin C Transporters / genetics
  • Sodium-Coupled Vitamin C Transporters / metabolism*
  • Transcription, Genetic


  • RNA, Heterogeneous Nuclear
  • RNA, Messenger
  • SLC23A2 protein, human
  • Slc23a2 protein, mouse
  • Sodium-Coupled Vitamin C Transporters
  • Ethanol
  • Ascorbic Acid