A5026158271- Drug Transport and Resistance Mechanisms
- Amino Acid Enzymes and Metabolism
- Pharmacological Effects and Toxicity Studies
- Antibiotics Pharmacokinetics and Efficacy
- Barrier Structure and Function Studies
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Trace Elements in Health
- Alzheimer's disease research and treatments
- Diet and metabolism studies
- Retinal Diseases and Treatments
- Pharmacogenetics and Drug Metabolism
- Epilepsy research and treatment
- Biochemical effects in animals
- Pancreatic function and diabetes
- Cholesterol and Lipid Metabolism
- Muscle metabolism and nutrition
- Protein Interaction Studies and Fluorescence Analysis
- Welding Techniques and Residual Stresses
- Cancer, Hypoxia, and Metabolism
- Advanced Proteomics Techniques and Applications
- Receptor Mechanisms and Signaling
- Peroxisome Proliferator-Activated Receptors
- Lanthanide and Transition Metal Complexes
- Metabolomics and Mass Spectrometry Studies
University of Eastern Finland
2021-2025
Tohoku University
2014-2023
Tohoku Medical and Pharmaceutical University
1996-2022
Tohoku Medical Megabank Organization
2018-2021
Target (United States)
2009-2020
Kurume University
2019
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2019
The University of Tokyo
1982-2018
Kagoshima University
2018
University of Tsukuba
2018
We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, blood-brain barrier (BBB). Brain microvessels were isolated from cortexes seven males (16-77 years old) 114 proteins was determined by means liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance showed most...
The purpose of the present study was to determine absolute protein expression levels multiple drug-metabolizing enzymes and transporters in 17 human liver biopsies, compare them with mRNA functional activities evaluate suitability three measures as parameters hepatic metabolism. Absolute 13 cytochrome P450 (P450) enzymes, NADPH-P450 reductase (P450R) 6 UDP-glucuronosyltransferase (UGT) microsomal fraction, 22 plasma membrane fraction were determined using liquid chromatography/tandem mass...
We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic (OST) transporters, 34 ATP-binding cassette (ABC) 51 metabolizing enzymes in human brain microvessels. used quantitative RT-PCR LC–MS/MS to examine isolated microvessels cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, SLC1A2/EAAT2 were main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 ABCA8 ABC quantified microvessels; ABCG2/BCRP was 1.6-fold...
Human cerebral microvascular endothelial cell line hCMEC/D3 is an established model of the human blood–brain barrier (BBB). The purpose present study was to determine, by means quantitative targeted absolute proteomics, protein expression levels in cells multiple transporters, receptors and junction proteins for comparison with our previously reported findings isolated brain microvessels. Among 91 target molecules, 12 2 receptors, 1 membrane marker were at quantifiable plasma fraction cells....
Abstract Proteomics has opened a new horizon in biological sciences. Global proteomic analysis is promising technology for the discovery of thousands proteins, post-translational modifications, polymorphisms, and molecular interactions variety systems. The activities roles identified proteins must also be elucidated, but this complicated by inability conventional methods to yield quantitative information protein expression. Thus, systems remain “black boxes”. Quantitative targeted absolute...
Although tight-junctions (TJs) at the blood-brain barrier (BBB) are important to prevent non-specific entry of compounds into CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose this study was therefore identify molecules, which regulate occludin expression, derived from astrocytes and pericytes that ensheathe brain microvessels by using conditionally immortalized adult rat capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) pericyte (TR-PCT1) cell...
Nitric oxide (NO) is involved in leukostasis and blood-retinal barrier (BRB) breakdown the early stages of diabetic retinopathy (DR), but it unclear which NO synthase (NOS) isoforms are primarily involved. In this study, authors aimed to clarify involvement constitutive (eNOS, nNOS) inducible NOS (iNOS) mechanisms underlying NO-mediated BRB breakdown.Diabetes was induced with streptozotocin for 2 weeks. Mice were treated a inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), shows...
Chronic hyperglycemia and activation of receptor for advanced glycation end products (RAGE) are known risk factors microvascular disease development in diabetic retinopathy. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor antioxidant thioredoxin (TRX), plays a causative role diabetes its vascular complications. Herein we investigate whether HG RAGE induce inflammation rat retinal endothelial cells (EC) under conditions culture through TXNIP epigenetic mechanisms play...
A brain efflux index method has been developed to characterize an transport system for substrates from the cerebrum circulating blood across blood-brain barrier. The value is defined as relative amount of test drug effluxed compared with that a reference compound, [14C]carboxylinulin, which limited barrier permeability. Microinjection 0.2, 0.5 or 1.0 microliter into parietal cortex area 2 region was found be appropriate procedure obtaining high recovery and restricting compound ipsilateral...
Abstract Renal impairment is associated with CNS dysfunctions and the accumulation of uremic toxins, such as indoxyl sulfate, in blood. To evaluate relevance sulfate to dysfunctions, we investigated brain‐to‐blood transport at blood–brain barrier (BBB) using Brain Efflux Index method. [ 3 H]Indoxyl undergoes efflux an rate 1.08 × 10 −2 /min, process saturable a K m 298 µ . This inhibited by para ‐aminohippuric acid, probenecid, benzylpenicillin, cimetidine toxinins, hippuric acidand...
The purpose of this study was to characterize blood-brain barrier (BBB) transport oxycodone, a cationic opioid agonist, via the pyrilamine transporter, putative organic cation using conditionally immortalized rat brain capillary endothelial cells (TR-BBB13). Oxycodone and [<sup>3</sup>H]pyrilamine were both transported into TR-BBB13 in temperature- concentration-dependent manner with <i>K</i><sub>m</sub> values 89 28 μM, respectively. initial uptake oxycodone significantly enhanced by...
Abstract Tight junctions (TJs) are an important component of the blood‐brain barrier, and claudin‐1, ‐3, ‐5 ‐12 have been reported to be localized at TJs brain capillary endothelial cells (BCECs). To understand contribution each claudin subtype TJ formation, we measured mRNA expression levels subtypes (claudin‐1 ‐23) other relevant proteins in highly purified mouse BCECs. Mouse BCECs were labeled with anti‐platelet cellular adhesion molecule‐1 antibody 2.3 × 10 6 isolated from 15 mice by...
Evidence is mounting that proinflammatory and proapoptotic thioredoxin-interacting protein (TXNIP) has a causative role in the development of diabetes. However, there are no studies investigating TXNIP diabetic retinopathy (DR). Here, we show that, rats, expression hexosamine biosynthesis pathway (HBP) flux, which regulates TXNIP, elevated retina correlates well with induction inflammatory cyclooxygenase 2 (Cox-2) sclerotic fibronectin (FN). We blocked rat retinas by: (i) inhibiting HBP...
The objectives of this study were to establish pure blood-nerve barrier (BNB) and blood-brain (BBB)-derived pericyte cell lines human origin investigate their unique properties as barrier-forming cells. Brain peripheral nerve established via transfection with retrovirus vectors incorporating temperature-sensitive SV40 T antigen (tsA58) telomerase. These expressed several markers such α-smooth muscle actin, NG2, platelet-derived growth factor receptor β, whereas they did not express...