RGD Reference Report - Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins. - Rat Genome Database

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Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins.

Authors: Wu, Kuo-Chen  Lu, Ya-Hsuan  Peng, Yi-Hsuan  Hsu, Lih-Ching  Lin, Chun-Jung 
Citation: Wu KC, etal., J Neurochem. 2015 Dec;135(6):1178-88. doi: 10.1111/jnc.13363. Epub 2015 Oct 14.
RGD ID: 30309929
Pubmed: PMID:26376205   (View Abstract at PubMed)
DOI: DOI:10.1111/jnc.13363   (Journal Full-text)

Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation transporter that is highly expressed in the central nervous system. This study aimed to investigate the effect of lipopolysaccharide on PMAT expression at the blood-brain barrier and the interaction between PMAT and neurotoxins. As a result, PMAT mRNA was identified in brain microvessels (BMVs), brain microvascular endothelial cells (BMECs), astrocytes, and pericytes isolated from C57BL/6 mice and/or Wistar rats using RT-qPCR. The immunofluorescence staining confirmed the expression of PMAT protein in BMVs and striatum of C57BL/6 mice. Western blotting demonstrated its localization at the luminal and abluminal sides of BMECs. In C57BL/6 mice, PMAT protein was significantly increased in BMVs 24 h after an intraperitoneal injection of 3 mg/kg lipopolysaccharide. Lipopolysaccharide treatment also significantly increased PMAT expression in cerebral cortex and the striatum in a time-dependent manner, as well as the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ). In isolated cells, lipopolysaccharide treatment significantly increased PMAT mRNA in brain astrocytes and the BMECs co-cultured with astrocytes. In addition to 1-methyl-4-phenylpyridinium, the kinetic study indicated that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-benzyl-TIQ are substrates of human PMAT. These findings suggest that inflammation can change PMAT expression at the blood-brain barrier, which may affect PMAT-mediated transport of neurotoxins. We demonstrated the expression of plasma membrane monoamine transporter (PMAT; mRNA or protein) at several subunits of the blood-brain barrier. Lipopolysaccharide treatment can significantly increase the expression of PMAT in vivo (in brain microvessels, cerebral cortex, and the striatum of C57BL/6 mice) and in vitro (in brain astrocytes and brain microvascular endothelial cells co-cultured with astrocytes). Lipopolysaccharide treatment also increased the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ) in mice, where 1-benzyl-TIQ competitively inhibited 1-methyl-4-phenylpyridinium (MPP(+)) uptake in MDCK-human PMAT (hPMAT) cells and its uptake in MDCK-hPMAT is concentration dependent.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane located_inIDA 30309929PMID:26376205ARUK-UCL 
basolateral plasma membrane located_inIDA 30309929PMID:26376205ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Slc29a4  (solute carrier family 29 member 4)


Additional Information