Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors
Article first published online: 25 FEB 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 117, Issue 2, pages 333–345, April 2011
How to Cite
Uchida, Y., Ohtsuki, S., Katsukura, Y., Ikeda, C., Suzuki, T., Kamiie, J. and Terasaki, T. (2011), Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors. Journal of Neurochemistry, 117: 333–345. doi: 10.1111/j.1471-4159.2011.07208.x
- Issue published online: 1 APR 2011
- Article first published online: 25 FEB 2011
- Accepted manuscript online: 3 FEB 2011 11:59AM EST
- Received October 7, 2010; revised manuscript received January 12, 2011; accepted January 28, 2011.
- human blood–brain barrier;
- liquid chromatography–tandem mass spectrometry;
- quantitative targeted absolute proteomics;
- species difference;
J. Neurochem. (2011) 117, 333–345.
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/μg 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/μg 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/μg 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.