RGD Reference Report - Endotoxin-induced inflammation down-regulates L-type amino acid transporter 1 (LAT1) expression at the blood-brain barrier of male rats and mice. - Rat Genome Database

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Endotoxin-induced inflammation down-regulates L-type amino acid transporter 1 (LAT1) expression at the blood-brain barrier of male rats and mice.

Authors: Wittmann, Gábor  Mohácsik, Petra  Balkhi, Mumtaz Yaseen  Gereben, Balázs  Lechan, Ronald M 
Citation: Wittmann G, etal., Fluids Barriers CNS. 2015 Sep 4;12:21. doi: 10.1186/s12987-015-0016-8.
RGD ID: 151361133
Pubmed: PMID:26337286   (View Abstract at PubMed)
PMCID: PMC4559167   (View Article at PubMed Central)
DOI: DOI:10.1186/s12987-015-0016-8   (Journal Full-text)


BACKGROUND: We recently reported that bacterial lipopolysaccharide (LPS)-induced inflammation decreases the expression of the primary thyroid hormone transporters at the blood-brain barrier, organic anion-transporting polypeptide 1c1 (OATP1c1) and monocarboxylate transporter 8 (MCT8). L-type amino acid transporters 1 and 2 (LAT1 & LAT2) are regarded as secondary thyroid hormone transporters, and are expressed in cells of the blood-brain or blood-cerebrospinal fluid barrier and by neurons. The purpose of this study was to examine the effect of LPS-induced inflammation on the expression of LAT1 and LAT2, as these may compensate for the downregulation of OATP1c1 and MCT8.
METHODS: LPS (2.5 mg/kg body weight) was injected intraperitoneally to adult, male, Sprague-Dawley rats and C57Bl/6 mice, which were euthanized 2, 4, 9, 24 or 48 h later. LAT1 and LAT2 mRNA expression were studied on forebrain sections using semiquantitative radioactive in situ hybridization. LAT1 protein levels in brain vessels were studied using LAT1 immunofluorescence. Statistical comparisons were made by the non-parametric Kruskal-Wallis and Dunn's tests.
RESULTS: In both species, LAT1 mRNA decreased in brain blood vessels as soon as 2 h after LPS injection and was virtually undetectable at 4 h and 9 h. During recovery from endotoxemia, 48 h after LPS injection, LAT1 mRNA in brain vessels increased above control levels. A modest but significant decrease in LAT1 protein levels was detected in the brain vessels of mice at 24 h following LPS injection. LPS did not affect LAT1 and LAT2 mRNA expression in neurons and choroid plexus epithelial cells.
CONCLUSIONS: The results demonstrate that LPS-induced inflammation rapidly decreases LAT1 mRNA expression at the blood-brain barrier in a very similar manner to primary thyroid hormone transporters, while changes in LAT1 protein level follow a slower kinetics. The data raise the possibility that inflammation may similarly down-regulate other blood-brain barrier transport systems at the transcriptional level. Future studies are required to examine this possibility and the potential pathophysiological consequences of inflammation-induced changes in blood-brain barrier transport functions.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Endotoxemia  ISOSlc7a5 (Rattus norvegicus)151361133; 151361133 RGD 
Endotoxemia  IEP 151361133 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc7a5  (solute carrier family 7 member 5)

Genes (Mus musculus)
Slc7a5  (solute carrier family 7 (cationic amino acid transporter, y+ system), member 5)

Genes (Homo sapiens)
SLC7A5  (solute carrier family 7 member 5)


Additional Information