Document Detail

Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiologically relevant source of ascorbic acid in the joint.
MedLine Citation:
PMID:  16142743     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To evaluate the dehydroascorbate (DHA) transport mechanisms in human chondrocytes. METHODS: The transport of L-(14)C-DHA in human chondrocytes was analyzed under various conditions, including the use of RNA interference (RNAi), to determine the role of glucose transporter 1 (GLUT-1) and GLUT-3 in L-14C-DHA transport and to evaluate the effects of physiologically relevant oxygen tensions on L-14C-DHA transport. In order to estimate the contributions of reduced ascorbic acid (AA) and DHA to intracellular ascorbic acid (Asc), the quantities of AA and DHA were measured in synovial fluid samples from osteoarthritis (OA) patients and compared with the reported levels in rheumatoid arthritis (RA) patients. RESULTS: DHA transport in human chondrocytes was glucose-sensitive, temperature-dependent, cytochalasin B-inhibitable, modestly stereoselective for L-DHA, and up-regulated by low oxygen tension. Based on the RNAi results, GLUT-1 mediated, at least in part, the uptake of DHA, whereas GLUT-3 had a minimal effect on DHA transport. DHA constituted a mean 8% of the total Asc in the synovial fluid of OA joints, in contrast to 80% of the reported total Asc in RA joints. CONCLUSION: We provide the first evidence that chondrocytes transport DHA via the GLUTs and that this transport mechanism is modestly selective for L-DHA. In the setting of up-regulated DHA transport at low oxygen tensions, DHA would contribute 26% of the total intracellular Asc in OA chondrocytes and 94% of that in RA chondrocytes. These results demonstrate that DHA is a physiologically relevant source of Asc for chondrocytes, particularly in the setting of an inflammatory arthritis, such as RA.
Amy L McNulty; Thomas V Stabler; Thomas P Vail; Gary E McDaniel; Virginia B Kraus
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  52     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-12     Completed Date:  2005-11-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2676-85     Citation Subset:  AIM; IM    
Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Arthritis, Rheumatoid / metabolism*,  pathology
Ascorbic Acid / metabolism
Biological Transport / drug effects
Cartilage, Articular / cytology,  metabolism*
Cell Hypoxia / drug effects,  physiology
Cells, Cultured
Chondrocytes / drug effects,  metabolism*,  pathology
Chromatography, High Pressure Liquid
Dehydroascorbic Acid / metabolism*
Gene Expression
Knee Joint / metabolism*,  pathology
Monosaccharide Transport Proteins / metabolism
Osteoarthritis, Knee / metabolism*,  pathology
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Monosaccharide Transport Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 490-83-5/Dehydroascorbic Acid; 50-81-7/Ascorbic Acid

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