Journal
JOURNAL OF NEUROCHEMISTRY
Volume 117, Issue 2, Pages 333-345Publisher
WILEY
DOI: 10.1111/j.1471-4159.2011.07208.x
Keywords
human blood-brain barrier; liquid chromatography-tandem mass spectrometry; quantitative targeted absolute proteomics; receptors; species difference; transporters
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Funding
- Japan Society for the Promotion of Science (JSPS) [20.7291]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [17081002]
- New Energy and the Industrial Technology Development Organization (NEDO) of Japan
- [18109002]
- Grants-in-Aid for Scientific Research [23790170, 17081002] Funding Source: KAKEN
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P>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 (16-77 years 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 (8.14 fmol/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 (6.06 fmol/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 (0.195 fmol/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.
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