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Quantitative targeted absolute proteomics of human bloodabrain barrier transporters and receptors

We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77years old) and protein expression of 1...

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Bibliographic Details
Published in:Journal of neurochemistry 2011-04, Vol.117 (2), p.333-345
Main Authors: Uchida, Yasuo, Ohtsuki, Sumio, Katsukura, Yuki, Ikeda, Chiemi, Suzuki, Takashi, Kamiie, Junichi, Terasaki, Tetsuya
Format: Article
Language:English
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Summary:We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14fmol/ mu g protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06fmol/ mu g protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195fmol/ mu g protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.Original Abstract: J. Neurochem. (2011) 117, 333-345.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2011.07208.x