Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors
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 ye...
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| Published in | Journal of neurochemistry Vol. 117; no. 2; pp. 333 - 345 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.04.2011
Wiley-Blackwell |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | 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. J. Neurochem. (2011) 117, 333-345. Abstract 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/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 (6.06fmol/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 (0.195fmol/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. 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.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. 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. |
| Author | Ohtsuki, Sumio Ikeda, Chiemi Katsukura, Yuki Suzuki, Takashi Kamiie, Junichi Terasaki, Tetsuya Uchida, Yasuo |
| Author_xml | – sequence: 1 givenname: Yasuo surname: Uchida fullname: Uchida, Yasuo – sequence: 2 givenname: Sumio surname: Ohtsuki fullname: Ohtsuki, Sumio – sequence: 3 givenname: Yuki surname: Katsukura fullname: Katsukura, Yuki – sequence: 4 givenname: Chiemi surname: Ikeda fullname: Ikeda, Chiemi – sequence: 5 givenname: Takashi surname: Suzuki fullname: Suzuki, Takashi – sequence: 6 givenname: Junichi surname: Kamiie fullname: Kamiie, Junichi – sequence: 7 givenname: Tetsuya surname: Terasaki fullname: Terasaki, Tetsuya |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24061724$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21291474$$D View this record in MEDLINE/PubMed |
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| Keywords | Cerebral cortex Membrane protein Breast disease Peptides transporters Central nervous system P Glycoprotein human blood―brain barrier Male Blood brain barrier Encephalon quantitative targeted absolute proteomics Biological receptor Human Drug Multidrug-resistant protein receptors Rodentia Breast cancer Malignant tumor Resistance species difference Mammary gland diseases Vertebrata Organic anion Membrane receptor Mammalia Mouse liquid chromatography―tandem mass spectrometry Cancer |
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| References | 2002; 59 1990; 10 2007; 426 1976; 69 1977; 28 1997; 230 1993; 20 2008; 36 2008; 107 2000; 294 1974 2008; 35 2005; 65 2008; 31 1972; 178 2004; 129 2009; 52 1966; 28 1986; 261 2008; 25 1983; 63 2008; 359 1994; 35 1993; 291 1998; 95 2004; 1018 2010; 7 2007; 24 2005; 77 2003; 44 2009; 24 2009; 65 2011 1991; 32 1989; 9 2002; 298 2009 1996; 16 1987; 18 1979; 135 2009; 77 1997; 763 2005; 19 1999; 274 2009; 9 2005; 6 1999; 113 2001; 38 2005; 2 2011; 100 2006; 100 2009; 37 2003; 23 e_1_2_8_28_1 e_1_2_8_24_1 e_1_2_8_47_1 e_1_2_8_26_1 e_1_2_8_49_1 e_1_2_8_3_1 e_1_2_8_5_1 e_1_2_8_7_1 e_1_2_8_9_1 e_1_2_8_20_1 e_1_2_8_43_1 e_1_2_8_22_1 e_1_2_8_45_1 e_1_2_8_41_1 e_1_2_8_60_1 e_1_2_8_17_1 e_1_2_8_19_1 e_1_2_8_13_1 e_1_2_8_36_1 e_1_2_8_15_1 e_1_2_8_38_1 e_1_2_8_57_1 e_1_2_8_32_1 e_1_2_8_55_1 e_1_2_8_11_1 e_1_2_8_34_1 e_1_2_8_53_1 e_1_2_8_51_1 Gao B. (e_1_2_8_18_1) 2000; 294 e_1_2_8_30_1 e_1_2_8_29_1 e_1_2_8_25_1 e_1_2_8_46_1 e_1_2_8_27_1 e_1_2_8_48_1 e_1_2_8_2_1 e_1_2_8_4_1 e_1_2_8_6_1 e_1_2_8_8_1 e_1_2_8_21_1 e_1_2_8_42_1 e_1_2_8_23_1 e_1_2_8_44_1 Wiesel F. A. (e_1_2_8_59_1) 1991; 32 e_1_2_8_40_1 e_1_2_8_39_1 e_1_2_8_14_1 e_1_2_8_35_1 e_1_2_8_16_1 e_1_2_8_37_1 e_1_2_8_58_1 e_1_2_8_10_1 e_1_2_8_31_1 e_1_2_8_56_1 e_1_2_8_12_1 e_1_2_8_33_1 e_1_2_8_54_1 e_1_2_8_52_1 e_1_2_8_50_1 |
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| Snippet | J. Neurochem. (2011) 117, 333–345.
We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in... We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is,... J. Neurochem. (2011) 117, 333-345. Abstract We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and... |
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| SubjectTerms | Adolescent Adult Age Factors Aged Animals Biological and medical sciences Biological Transport - physiology Blood Blood-Brain Barrier - metabolism Brain Brain - cytology Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Chromatography, Liquid - methods Fundamental and applied biological sciences. Psychology Gynecology. Andrology. Obstetrics human blood–brain barrier Humans liquid chromatography–tandem mass spectrometry Male Mammary gland diseases Medical sciences Membrane Proteins - metabolism Membrane Transport Proteins - metabolism Mice Middle Aged Neurons Proteomics Proteomics - methods quantitative targeted absolute proteomics receptors Receptors, Cell Surface - metabolism Rodents species difference Tandem Mass Spectrometry - methods transporters Tumors Vertebrates: nervous system and sense organs Young Adult |
| Title | Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors |
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