A5101800714- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Pharmacological Effects and Toxicity Studies
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
- Fungal Biology and Applications
- Cellular Mechanics and Interactions
- Plant Pathogens and Fungal Diseases
- Trace Elements in Health
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- Hippo pathway signaling and YAP/TAZ
- Lipid Membrane Structure and Behavior
- Plant tissue culture and regeneration
- Fungal Plant Pathogen Control
- Dental Health and Care Utilization
- Lipid metabolism and biosynthesis
- Nutrition and Health in Aging
- Advanced Fiber Laser Technologies
- Cardiac Ischemia and Reperfusion
- Metal complexes synthesis and properties
- TiO2 Photocatalysis and Solar Cells
- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Caveolin-1 and cellular processes
Kyoto University
2013-2024
Osaka Metropolitan University
2024
Musashino University
2024
Sungkyunkwan University
2021
Osaka City University
2021
Tokyo University of Technology
2016
Tohoku University
1994-2013
SPring-8
2010
Tokyo Metropolitan Institute of Medical Science
2010
Saga University
2002-2009
Significance P-glycoprotein exports various hydrophobic chemicals in an ATP-dependent manner, determines their absorption and distribution the body, is involved multidrug resistance (MDR) tumors. Understanding mechanism of transport important for designing drugs good bioavailability efficient cancer chemotherapy. We determined high-resolution crystal structures a eukaryotic homolog revealed detailed architecture its transmembrane domains, which contain exit gate substrates that opens to...
MDR1 (multidrug resistance 1)/P-glycoprotein is an ATP-driven transporter which excretes a wide variety of structurally unrelated hydrophobic compounds from cells. It suggested that drugs bind to directly the lipid bilayer and cholesterol in also interacts with MDR1. However, effects on drug–MDR1 interactions are still unclear. To examine these effects, human was expressed insect cells purified. The purified protein reconstituted proteoliposomes containing various concentrations enzymatic...
Abstract P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, largely due to lack high-resolution structural information regarding alternate conformational states molecule. Here we report pair structures homodimeric P-glycoprotein: an outward-facing state with bound nucleotide and inward-facing apo state, at resolutions 1.9 Å 3.0 Å, respectively....
Objective: Although tooth loss causes a decrease in masticatory ability, which may influence nutritional status, and impair an individual's general health including physical activity, little is known whether chewing ability could result deterioration fitness very elderly population. Thus, the present study evaluated relationship of or teeth number with measures sample 80‐years‐old Japan. Design: Cross‐sectional survey. Subjects methods: A total 1282 people who were 80‐years old resided...
The relationship between physical fitness and dental health status in elderly adults is still unknown. purpose of the present study to examine occlusal condition natural teeth population. sample consisted 591 individuals aged 70 years 158 80 selected from registry residents Niigata city.Hand grip strength (kg), leg extensor power (watts), stepping rate (time per 10 seconds), one-leg standing time with eyes open (seconds) were measured. Eichner index was used as a measurement condition. It...
ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein metabolism. Apolipoprotein A-I binds to ABCA1 cellular phospholipids, mainly phosphatidylcholine, are loaded onto apoA-I form pre-β (HDL). It is proposed that translocates phospholipids directly or indirectly HDL. To explore the mechanism of ABCA1-mediated HDL formation, we expressed human insect Sf9 cells purified it. Trypsin limited-digestion detergent-soluble suggested it...
ABSTRACT Extracellular matrix (ECM) stiffness regulates the lineage commitment of mesenchymal stem cells (MSCs). Although sense ECM through focal adhesions, how and regulate stiffness-dependent differentiation remains largely unclear. In this study, we show that cytoskeletal adhesion protein vinculin plays a critical role in adipocyte MSCs. ST2 mouse MSCs differentiate into adipocytes osteoblasts an manner. We find rigid increases amount cytoskeleton-associated promotes nuclear localization...
We combine spectroscopic ellipsometry (SE), Fourier transform infrared spectroscopy (FT-IR), kinetic Monte Carlo simulations (KMC) and convex corner undercutting analysis in order to characterize explain the effect of addition small amounts surfactant alkaline aqueous solutions, such as Triton X-100 tetra methyl ammonium hydroxide (TMAH). propose that is adsorbed at silicon–etchant interface a thin layer, acting filter moderates surface reactivity by reducing amount reactant molecules reach...
ATP-binding cassette protein G1 (ABCG1) is important for the formation of HDL. However, biochemical properties ABCG1 have not been reported, and mechanism how involved in HDL remains unclear. We established a procedure to express purify human using suspension-adapted cell FreeStyle293-F. ABCG1, fused at C terminus with green fluorescent Flag-peptide, was solubilized n-dodecyl-β-D-maltoside purified via single round Flag-M2 antibody affinity chromatography. The reconstituted liposome various...
Although extracellular matrix (ECM) stiffness is an important factor of the microenvironment and known to direct lineage specification stem cells affect cancer progression, molecular mechanisms that sense ECM have not yet been elucidated. In this study, we show proline-rich linker (PRL) region vinculin PRL region-binding protein vinexin are involved in sensing substrates. A rigid substrate increases cytoskeleton-associated vinculin, fraction stably localizing at focal adhesions (FAs) larger...
Vinexin, c-Cbl associated protein (CAP) and Arg-binding 2 (ArgBP2) constitute an adaptor family called the vinexin (SORBS) that is targeted to focal adhesions (FAs). Although numerous studies have focused on each of SORBS proteins partially elucidated their involvement in mechanotransduction, a comparative analysis function has not been well addressed. Here, we established mouse embryonic fibroblasts individually expressed analysed functions identical cell context. Both vinexin-α CAP...
Abstract The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) apolipoprotein A-I (apoA-I) play essential roles nascent HDL formation, but controversy persists regarding the mechanism by which is generated. In “direct loading model”, apoA-I acquires lipids directly from ABCA1 while it bound to transporter. By contrast, “indirect specific membrane domains created ABCA1. this...
ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze characteristics these transporters, we examined compared their distributions activity on plasma membrane. The mediated by ABCA1 but not ABCG4, was affected a reduction cellular sphingomyelin levels. Detergent solubility gradient density ultracentrifugation assays indicated ABCA1, were distributed to domains solubilized Triton X-100 Brij 96, resistant...
Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined of with decline 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom were available from comprehensive health examinations conducted 2010 2013.Based on a baseline full-mouth periodontal examination, severe was defined using Centers Disease Control Prevention/American Academy Periodontology...
We report an estimation of the injected mass composition ultrahigh energy cosmic rays (UHECRs) at energies higher than 10 EeV. The is inferred from energy-dependent sky distribution UHECR events observed by Telescope Array surface detector comparing it to Large Scale Structure local Universe. In case negligible extragalactic magnetic fields (EGMFs), results are consistent with a relatively heavy E∼10 EeV that becomes lighter up E∼100 EeV, while E>100 very heavy. latter true even in presence...
Vα14 TCR expressing invariant NK T (iNKT) cells recognize α-galactosylceramide (αGC)/CD1d complex and produce large amounts of various cytokines before the onset adaptive immunity. After stimulation with a high dose (2-5 μg) αGC in vivo, iNKT spleen liver become anergic terms proliferation cytokine production to subsequent stimulation. In this study, we monitor how anergy is induced. Anergized dramatically reduced expression IL-2Rα, exogenous IL-2 restored ability proliferate IL-4 but not...
ABCA1 plays a major role in HDL metabolism. Cholesterol secretion by is dependent on the presence of extracellular acceptors, such as lipid-free apolipoprotein A-I (apoA-I). However, importance direct interaction between apoA-I and formation remains unclear. In contrast, ABCB4 mediates phospholipids cholesterol sodium taurocholate (NaTC) but not apoA-I. this study, we analyzed binding NaTC-dependent lipid efflux ABCA1. mediated NaTC well an ATP-dependent manner. The Tangier disease mutation...
Human P-glycoprotein (P-gp), which conveys multidrug resistance, is an ATP-dependent drug efflux pump that transports a wide variety of structurally unrelated compounds out cells. P-gp possesses 'linker region' approximately 75 amino acids connects two homologous halves, each contain transmembrane domain followed by nucleotide-binding domain. To investigate the role linker region, purified human was cleaved proteases at region and then compared with native P-gp. Based on verapamil-stimulated...
ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. contains disulfide bond(s) between its N- C-terminal halves, but it remains unclear whether bond formation is important for the functions of which cysteines are involved formation. To answer these questions, we constructed >30 mutants 16 extracellular domain (ECD) were replaced with serines examined formation, apoA-I binding, HDL mutants. From single cysteine replacements, two (Cys75 Cys309)...
ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high-density lipoprotein (HDL) metabolism. Although it is predicted that apolipoprotein A-I (apoA-I) directly binds to ABCA1, the physiological importance of this interaction still controversial conformation required for apoA-I binding unclear. In study, two nucleotide-binding domains (NBD) ABCA1 was determined by inserting TEV protease recognition sequence linker region ABCA1. Analyses ATP occlusion...
The extracellular matrix (ECM) is a major regulator of cell behavior. Recent studies have indicated the importance physical properties ECM, including its stiffness, for migration and differentiation. Using actomyosin-generated forces, cells pull ECM sense stiffness via cell-ECM adhesion structures called focal adhesions (FAs). Vinculin, an actin-binding FA protein, has emerged as player in FA-mediated mechanotransduction. Although vinculin important sensing role binding to actin...