Document Detail


Characterization and astrocytic modulation of system L transporters in brain microvasculature endothelial cells.
MedLine Citation:
PMID:  18210381     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brain trafficking of amino acids is mainly mediated by amino acids transport machineries of the blood-brain barrier (BBB), where astrocytes play a key maintenance role. However, little is known about astrocytes impacts on such transport systems, in particular system L that consists of large and small neutral amino acids (NAAs) transporters, that is, LAT1/4F2hc and LAT2/4F2hc, respectively. In the current investigation, functionality and expression of system L were studied in the immortalized mouse brain microvascular endothelial b.End3 cells cocultured with astrocytes or treated with astrocyte-conditioned media (ACM). LAT2/4F2hc mediated luminal uptake of L-phenylalanine and L-leucine resulted in significantly decreased affinity of system L in b.End3 cells treated with ACM, while LAT2/4F2hc mediated luminal uptake of L-alanine remained unchanged. Gene expression analysis revealed marked upregulation of LAT1 and 4F2hc, but downregulation of LAT2 in b.End3 cells cultured with ACM. The basal to apical transport of L-phenylalanine and L-alanine appeared to be significantly greater than that of the apical to basal direction in b.End3 cells indicating an efflux functionality of system L. No marked influence was observed for transport of L-phenylalanine in b.End3 cells cocultured with astrocytes, while a slight decrease was seen for L-alanine in the basal to apical direction. Based on our findings, we propose that system L functions as influx and/or efflux transport machinery displaying a greater propensity for the outward transport of large and small NAAs. Astrocytes appeared to modulate the transcriptic expression and uptake functionalities of system L, but not the transport activities.
Authors:
Yadollah Omidi; Jaleh Barar; Somaieh Ahmadian; Hamid Reza Heidari; Mark Gumbleton
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell biochemistry and function     Volume:  26     ISSN:  1099-0844     ISO Abbreviation:  Cell Biochem. Funct.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-14     Completed Date:  2008-05-15     Revised Date:  2009-08-12    
Medline Journal Info:
Nlm Unique ID:  8305874     Medline TA:  Cell Biochem Funct     Country:  England    
Other Details:
Languages:  eng     Pagination:  381-91     Citation Subset:  IM    
Affiliation:
Pharmaceutical Cell Biology, Welsh School of Pharmacy, Cardiff University, Cardiff, UK. yomidi@tbzmed.ac.ir
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport System y+ / genetics,  metabolism*
Amino Acids / pharmacology
Animals
Antigens, CD98 Light Chains
Astrocytes / cytology,  drug effects,  metabolism*
Biological Transport / drug effects
Blood-Brain Barrier / cytology,  drug effects
Brain / blood supply*,  cytology*,  drug effects
Cells, Cultured
Endothelial Cells / cytology,  drug effects,  metabolism*
Gene Expression Regulation / drug effects
Isomerism
Kinetics
Mice
RNA, Messenger / genetics,  metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
Sodium / pharmacology
Temperature
Time Factors
Chemical
Reg. No./Substance:
0/Amino Acid Transport System y+; 0/Amino Acids; 0/Antigens, CD98 Light Chains; 0/RNA, Messenger; 0/SLC7A8 protein, mouse; 0/Slc7a7 protein, mouse; 7440-23-5/Sodium

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


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