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

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

Author information

1
Department of Medicine, University of California, Irvine, California; Department of Physiology, University of California, Irvine, California; Department of Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California.
2
Department of Medicine, University of California, Irvine, California; Department of Physiology, University of California, Irvine, California; Department of Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California hmsaid@uci.edu.

Abstract

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

PMID:
27122159
PMCID:
PMC4967129
DOI:
10.1152/ajpcell.00042.2016
[Indexed for MEDLINE]
Free PMC Article

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