Document Detail


Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes.
MedLine Citation:
PMID:  17928533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study reports on the functional expression of a specific, high-affinity carrier-mediated mechanism for the transport of niacin (nicotinic acid) in human liver cells. Both human-derived liver HepG2 cells and human primary hepatocytes were used as models in these investigations. The initial rate of transport of nicotinic acid into HepG2 cells was found to be acidic pH, temperature, and energy dependent; it was, however, Na(+) independent in nature. Evidence for the existence of a carrier-mediated system that is specific for [(3)H]nicotinic acid transport was found and included the following: 1) saturability as a function of concentration with an apparent K(m) of 0.73 +/- 0.16 microM and V(max) of 25.02 +/- 1.45 pmol.mg protein(-1).3 min(-1), 2) cis-inhibition by unlabeled nicotinic acid and nicotinamide but not by unrelated organic anions (lactate, acetate, butyrate, succinate, citrate, and valproate), and 3) trans-stimulation of [(3)H]nicotinic acid efflux by unlabeled nicotinic acid. Transport of the vitamin into human primary hepatocytes occurs similarly via an acidic pH-dependent and specific carrier-mediated process. Inhibitors of the Ca(2+)-calmodulin-mediated pathway (but not modulators of the PKC-, PKA-, and protein tyrosine kinase-mediated pathways) inhibited nicotinic acid transport into both HepG2 cells and human primary hepatocytes. Maintenance of HepG2 cells (for 48 h) in growth medium oversupplemented with nicotinic acid (or nicotinamide) did not affect the subsequent transport of [(3)H]nicotinic acid into HepG2 cells. These results show, for the first time, the existence of a specific and regulated membrane carrier-mediated system for nicotinic acid transport in human liver cells.
Authors:
Hamid M Said; Svetlana M Nabokina; Krishnaswamy Balamurugan; Zainab M Mohammed; Cecilia Urbina; Moti L Kashyap
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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:  2007-10-10
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  293     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-12     Completed Date:  2008-03-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C1773-8     Citation Subset:  IM    
Affiliation:
Veterans Affairs Medical Center, Long Beach, CA 90822, USA. hmsaid@uci.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Anions / metabolism
Calcium Signaling / physiology
Cell Culture Techniques
Cell Line
Female
Hepatocytes / metabolism*
Humans
Hydrogen-Ion Concentration
Liver / metabolism
Male
Middle Aged
Niacin / metabolism*
Sodium / metabolism
Grant Support
ID/Acronym/Agency:
DK56061/DK/NIDDK NIH HHS; DK58057/DK/NIDDK NIH HHS; DK64165/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Anions; 59-67-6/Niacin; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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