東北大学 · 의학
유치다 요시오 교수가 이끄는 연구실은 혈뇌장벽과 혈뇌세액장벽의 단백질 발현 프로파일을 정량적으로 분석하는 데 전문성을 가진다. 주로 질량분석 기반 정량형 타겟 단백질체학(quantitative targeted absolute proteomics)을 활용해 뇌의 병변과 관련된 수송체, 수용체, 밀착접합 단백질의 절대 농도를 규명하며, 알츠하이머병과 같은 신경퇴행성 질환에서의 혈류장벽 기능 이상을 기초적으로 밝혀내는 데 초점을 맞추고 있다. 특히 인간과 실험동물의 뇌 혈관에서 단백질 발현의 종류와 양을 비교 분석함으로써 뇌내 약물 전달 메커니즘을 규명하고자 한다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
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 tra
Proteomics has opened a new horizon in biological sciences. Global proteomic analysis is a promising technology for the discovery of thousands of proteins, post-translational modifications, polymorphisms, and molecular interactions in a variety of biological systems. The activities and roles of the identified proteins must also be elucidated, but this is complicated by the inability of conventional proteomic methods to yield quantitative information for protein expression. Thus, a variety of bio
The purpose of this study was to determine absolute protein expression levels of transporters in rat choroid plexus, that is, the blood-cerebrospinal fluid barrier, and to compare them with the levels in the human choroid plexus. Plasma membrane fractions were prepared from pooled, freshly isolated choroid plexuses of 30 male Wistar rats and from frozen choroid plexus of one male human donor. Protein expression levels of 54 rat and 121 human molecules were measured, using a quantitative targeted
The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as deter
The cerebrovascular-specific molecular mechanism in Alzheimer's disease (AD) was investigated by employing comprehensive and accurate quantitative proteomics. Highly purified brain capillaries were isolated from cerebral gray and white matter of four AD and three control donors, and examined by SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Of the 29 ribosomal proteins that were quantified, 28 (RPLP0, RPL4, RPL6, RPL7A, RPL8, RPL10A, RPL11, RPL12, RPL14
This work was designed to clarify the absolute abundances of transporters and receptors at different cerebral regions of the blood-brain barriers (BBB) and blood-spinal cord barrier (BSCB) in humans and rats, using physiologically relevant units (pmol/g tissue and fmol/cm<sup>2</sup>); 39 and 29 proteins including tight-junction proteins and markers were quantified in human and rat capillary samples, respectively. Protein expression levels of almost all proteins were identical within a 2-fold ra
A proton-coupled organic cation (H<sup>+</sup>/OC) antiporter working at the blood-brain barrier (BBB) in humans and rodents is thought to be a promising candidate for the efficient delivery of cationic drugs to the brain. Therefore, it is important to identify the molecular entity that exhibits this activity. Here, for this purpose, we established the <b>P</b>roteomics-based <b>I</b>dentification of transporter by <b>C</b>rosslinking substrate in <b>K</b>eyhole (PICK) method, which combines pho
