Document Detail


Promoter analysis of the human ascorbic acid transporters SVCT1 and 2: mechanisms of adaptive regulation in liver epithelial cells.
MedLine Citation:
PMID:  20471816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ascorbic acid, the active form of vitamin C, is a vital antioxidant in the human liver, yet the molecular mechanisms involved in the regulation of ascorbic acid transporters [human sodium-dependent vitamin C transporters (hSVCT) 1 and 2] in liver cells are poorly understood. Therefore, we characterized the minimal promoter regions of hSVCT1 and 2 in cultured human liver epithelial cells (HepG2) and examined the effects of ascorbic acid deprivation and supplementation on activity and regulation of the transport systems. Identified minimal promoters required for basal activity were found to include multiple cis regulatory elements, whereas mutational analysis demonstrated that HNF-1 sites in the hSVCT1 promoter and KLF/Sp1 sites in the hSVCT2 promoter were essential for activities. When cultured in ascorbic acid deficient or supplemented media, HepG2 cells demonstrated significant (P<.01) and specific reciprocal changes in [(14)C]-Ascorbic acid uptake, and in hSVCT1 mRNA and protein levels as well as hSVCT1 promoter activity. However, no significant changes in hSVCT2 expression or promoter activity were observed during ascorbic acid deficient or supplemented conditions. We mapped the ascorbic acid responsive region in the hSVCT1 promoter and determined that HNF-1 sites are important for the adaptive regulation response. The results of these studies further characterize the hSVCT1 and 2 promoters establish that ascorbic acid uptake by human liver epithelial cells is adaptively regulated and show that transcriptional mechanisms via HNF-1 in the hSVCT1 promoter may, in part, be involved in this regulation.
Authors:
Jack C Reidling; Stanley A Rubin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-05-14
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  22     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-06-28     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  344-50     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Descriptor/Qualifier:
Ascorbic Acid / metabolism,  pharmacology
Ascorbic Acid Deficiency / physiopathology
Gene Expression Regulation
Hep G2 Cells
Hepatocyte Nuclear Factor 1 / physiology
Humans
Organic Anion Transporters, Sodium-Dependent / genetics*
Promoter Regions, Genetic / physiology
Sodium-Coupled Vitamin C Transporters
Symporters / genetics*
Grant Support
ID/Acronym/Agency:
DK73032/DK/NIDDK NIH HHS; K01 DK073032/DK/NIDDK NIH HHS; K01 DK073032-05/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Organic Anion Transporters, Sodium-Dependent; 0/SLC23A1 protein, human; 0/Sodium-Coupled Vitamin C Transporters; 0/Symporters; 126548-29-6/Hepatocyte Nuclear Factor 1; PQ6CK8PD0R/Ascorbic Acid
Comments/Corrections

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