Document Detail


Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure.
MedLine Citation:
PMID:  21868632     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thiamin is important for normal function of pancreatic acinar cells, but little is known about its mechanism of uptake and about the effect of chronic alcohol use on the process. We addressed these issues using freshly isolated rat primary and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed thiamin uptake by both primary and cultured AR42J pancreatic acinar cells to be via a specific carrier-mediated mechanism and that both of the thiamin transporters 1 and 2 (THTR-1 and THTR-2) are expressed in these cells. Chronic alcohol feeding of rats was found to lead to a significant inhibition of carrier-mediated thiamin uptake by pancreatic acinar cells and was associated with a significant reduction in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels. Chronic exposure (96 h) of AR42J cells to alcohol also led to a significant decreased carrier-mediated thiamin uptake, an effect that was associated with a significant decrease in the activity of the human SLC19A2 and SLC19A3 promoters expressed in these cells. We also examined the effect of chronic alcohol feeding of rats on level of expression of key thiamin metabolizing enzymes (thiamin phosphokinase and thiamin pyrophosphatase) as well as on level of expression of the mitochondrial thiamin pyrophosphate transporter of pancreatic acinar cells and observed a significant inhibition in all these parameters. These results demonstrate for the first time that thiamin uptake by pancreatic acinar cells is via a carrier-mediated process and that both the THTR-1 as well as THTR-2 are expressed in these cells. Also, chronic alcohol feeding/exposure inhibits thiamin uptake process and the inhibition is, at least in part, being exerted at the transcriptional level. Furthermore, chronic alcohol feeding also negatively impacts intracellular parameters of thiamin metabolism in pancreatic acinar cells.
Authors:
Sandeep B Subramanya; Veedamali S Subramanian; V Thillai Sekar; Hamid M Said
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-08-25
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  301     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-31     Completed Date:  2011-12-15     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G896-904     Citation Subset:  IM    
Affiliation:
Department of Medicine and Physiology/Biophysics, University of California, Irvine, USA.
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MeSH Terms
Descriptor/Qualifier:
Acinar Cells / drug effects,  metabolism*
Alcohol Drinking / genetics,  metabolism*
Animals
Biological Transport / drug effects,  genetics
Cells, Cultured
Epithelial Cells / drug effects,  metabolism*
Ethanol / administration & dosage*
Male
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism
Rats
Rats, Wistar
Thiamine / metabolism*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
AA 018071/AA/NIAAA NIH HHS; DK 56061/DK/NIDDK NIH HHS; R01 AA018071-04/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 59-43-8/Thiamine; 64-17-5/Ethanol
Comments/Corrections

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