| Mechanism and regulation of folate uptake by pancreatic acinar cells: effect of chronic alcohol consumption. | |
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MedLine Citation:
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PMID: 20360131 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Folate plays an essential role in one-carbon metabolism, and a relationship exists between methyl group metabolism and pancreatic exocrine function. Little, however, is known about the mechanism(s) and regulation of folate uptake by pancreatic acinar cells and the effect of chronic alcohol use on the process. We addressed these issues using the rat-derived pancreatic acinar cell line AR42J and freshly isolated primary rat pancreatic acinar cells as models. We found [(3)H]folic acid uptake to be 1) temperature and pH dependent with a higher uptake at acidic than at neutral/alkaline pH; 2) saturable as a function of substrate concentration at both buffer pH 7.4 and 6.0; 3) inhibited by folate structural analogs and by anion transport inhibitors at both buffer pH 7.4 and 6.0; 4) trans-stimulated by unlabeled folate; 5) adaptively regulated by the prevailing extracellular folate level, and 6) inhibited by modulators of the cAMP/PKA-mediated pathway. Both the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT) were found to be expressed in AR42J and in primary pancreatic acinar cells, as well as in native human pancreas with expression of RFC being higher than PCFT. Chronic alcohol feeding of rats (4 wk; 36% of calories from ethanol) led to a significant decrease in folate uptake by freshly isolated primary pancreatic acinar cells compared with cells from pair-fed controls; this effect was associated with a parallel decrease in the level of expression of RFC and PCFT. These studies reveal that folate uptake by pancreatic acinar cells is via a regulated carrier-mediated process which may involve RFC and PCFT. In addition, chronic alcohol feeding leads to a marked inhibition in folate uptake by pancreatic acinar cells, an effect that is associated with reduction in level of expression of RFC and PCFT. |
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Authors:
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Hamid M Said; Lisa Mee; V Thillai Sekar; Balasubramaniem Ashokkumar; Stephen J Pandol |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-01 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 298 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G985-93 Citation Subset: IM |
Affiliation:
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VA Medical Center-151, Long Beach, CA 90822, USA. hmsaid@uci.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Drug Administration Schedule Ethanol / administration & dosage, metabolism*, toxicity* Folic Acid / metabolism* Humans Hydrogen-Ion Concentration Male Pancreas / cytology*, drug effects* Rats Rats, Sprague-Dawley Temperature |
| Grant Support | |
ID/Acronym/Agency:
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AA018071/AA/NIAAA NIH HHS; DK56061/DK/NIDDK NIH HHS; P50-AA11999/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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59-30-3/Folic Acid; 64-17-5/Ethanol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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