A5029131320- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Polyamine Metabolism and Applications
- Drug Transport and Resistance Mechanisms
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Biopolymer Synthesis and Applications
- Chemical Synthesis and Analysis
- Boron Compounds in Chemistry
- Lanthanide and Transition Metal Complexes
- Radiopharmaceutical Chemistry and Applications
- Plant nutrient uptake and metabolism
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Advanced Proteomics Techniques and Applications
- Molecular Sensors and Ion Detection
- Pancreatic function and diabetes
- Analytical Chemistry and Sensors
- Kidney Stones and Urolithiasis Treatments
- Ion Transport and Channel Regulation
- Plant Stress Responses and Tolerance
Osaka University
2016-2025
Bio-Medical Science (South Korea)
2021
Guangdong Pharmaceutical University
2020
Nara Medical University
2020
Gunma University
2020
Mitsubishi Tanabe Pharma Corporation
2016
Osaka Prefecture University
2016
Pharmac
2015
University Medical Center Groningen
2010-2011
University of Groningen
2010-2011
The efficacy of boron neutron capture therapy relies on the selective delivery carriers to malignant cells. p-Boronophenylalanine (BPA), a agent, has been proposed be localized cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters identify BPA transporters. Human were functionally expressed in Xenopus oocytes and examined for uptake kinetic parameters. roles characterized cancer cell lines. For quantitative assessment uptake, HPLC was used...
l-3-(18)F-α-methyl tyrosine ((18)F-FAMT) has been developed as a PET radiotracer for tumor imaging. Clinical studies have demonstrated the usefulness of (18)F-FAMT prediction prognosis and differentiation malignant tumors benign lesions. exhibits higher cancer specificity in peripheral organs than other amino acid tracers (18)F-FDG. The accumulation is strongly correlated with expression L-type transporter 1 (LAT1), an isoform system L highly upregulated cancers. In this study, we examined...
Significance Although molecular identification of transporters in mammals seems almost settled, some long-proposed still remain to be revealed. The second cystine transporter renal reabsorption is one such transporters. Its genetic defect has been proposed responsible for a type cystinuria distinct from that caused by the mutations already known transporter. In this study, we have found membrane protein SLC7A13 as with characteristics, and provided possible clue genetics previously...
Canagliflozin, a selective sodium/glucose cotransporter (SGLT) 2 inhibitor, suppresses the renal reabsorption of glucose and decreases blood level in patients with type diabetes. A characteristic canagliflozin is its modest SGLT1 inhibitory action intestine at clinical dosage. To reveal mechanism action, we investigated interaction SGLT2. Inhibition kinetics transporter-mediated uptake were examined human SGLT1- or SGLT2-expressing cells. Whole-cell patch-clamp recording was conducted to...
L-type amino acid transporter 1 (LAT1) is known as a cancer-type transporter. In cancer cells, LAT1 responsible for the cellular uptake of many essential acids including leucine that activates mechanistic/mammalian target rapamycin (mTOR), regulating cell growth. this study, we designed novel series inhibitors, SKN101–105, based on structure triiodothyronine (T3), blocker. The compounds consist core 2-amino-3-[3,5-dichloro-4-(naphthalene-1-methoxy)-phenyl]-propanoic and different...
Abstract Background Tumor angiogenesis is regarded as a rational anti-cancer target. The efficacy and indications of anti-angiogenic therapies in clinical practice, however, are relatively limited. Therefore, there still exists demand for revealing the distinct characteristics tumor endothelium that crucial pathological angiogenesis. L-type amino acid transporter 1 (LAT1) well known to be highly broadly upregulated cells support their growth proliferation. In this study, we aimed establish...
Glutamate is a pivotal excitatory neurotransmitter in mammalian brains, but excessive glutamate causes numerous neural disorders. Almost all extracellular retrieved by the glial transporter, Excitatory Amino Acid Transporter 2 (EAAT2), belonging to SLC1A family. However, some cancers, EAAT2 expression enhanced and resistance therapies metabolic disturbance. Despite its crucial roles, detailed structural information about has not been available. Here, we report cryo-EM structures of human...
L-type amino acid transporter 1 (LAT1) is a transmembrane protein responsible for transporting large neutral acids. While numerous LAT1-targeted compound delivery the brain and tumors have been investigated, their LAT1 selectivity often remains ambiguous despite high affinity. This study assessed of phenylalanine (Phe) analogs, focusing on structure-activity characteristics. We discovered that 2-iodo-L-phenylalanine (2-I-Phe), with an iodine substituent at position 2 in benzene ring,...
Polarized epithelial cells develop and maintain distinct apical basolateral surface domains despite a continuous flux of membranes between these domains. The Na(+)/H(+)exchanger NHE6 localizes to endosomes but its function is unknown. Here, we demonstrate that polarized hepatoma HepG2 express an NHE6.1 variant recycling colocalizes with transcytosing bulk membrane lipids. knockdown or overexpression decreases increases endosome pH, respectively, inhibits the maintenance apical, bile...
The layers of the epithelial syncytium, i.e., syncytiotrophoblasts, differentiate from chorionic trophoblasts via cell fusion and separate maternal fetal circulations in hemochorial placentas. L-type amino acid transporter 1 (LAT1) its covalently linked ancillary subunit 4F2hc are colocalized on both surfaces implying their roles transfer through placental barrier. In this study, LAT1 knockout, addition, revealed a novel role syncytiotrophoblast development. at midgestation was selectively...
In mammalian cells, four Na(+)/H(+) exchangers (NHE6 - NHE9) are localized to intracellular compartments. NHE6 and NHE9 predominantly sorting recycling endosomes, NHE7 the trans-Golgi network, NHE8 mid-trans-Golgi stacks. The unique localization of NHEs may contribute establishing organelle-specific pH values ion homeostasis in cells. Mechanisms underlying regulation targeting organellar largely unknown. We identified an interaction between RACK1 (receptor for activated C kinase 1), a...
Abstract Various physiological and pathological processes are accompanied with the alteration of pH at extracellular juxtamembrane region. Accordingly, methods to analyze cell surface have been demanded in biological medical sciences. In this study, we established a novel methodology for imaging using poly(ethylene glycol)-phospholipid (PEG-lipid) as core structure ratiometric fluorescent probes. PEG-lipid is synthetic amphiphilic polymer originally developed modification transplantation...
Abstract L‐type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral acids, is highly upregulated in various cancers. LAT1 supplies cancer cells with acids as substrates for enhanced biosynthetic and bioenergetic reactions stimulates signalling networks involved the regulation of survival, growth proliferation. inhibitors show anti‐cancer effects a representative compound, JPH203, under clinical evaluation. However, pharmacological impacts inhibition on...
Metastasis is the leading cause of mortality in cancer patients. L-type amino acid transporter 1 (LAT1, SLC7A5) a Na+-independent neutral highly expressed various cancers to support their growth. Although high LAT1 expression closely associated with metastasis, its role this process remains unclear. This study aimed investigate effect inhibition on metastasis using B16-F10 melanoma mouse models. Our results demonstrated that nanvuranlat (JPH203), high-affinity LAT1-selective inhibitor,...
L-type amino acid transporter 1 (LAT1, SLC7A5), overexpressed in various cancers, mediates the uptake of essential acids crucial for tumor growth. It has emerged as a promising target cancer therapy. Nanvuranlat (JPH203/KYT-0353), LAT1 inhibitor, shown antitumor activity preclinical studies and efficacy biliary tract during clinical trials. This study provides comprehensive pharmacological characterization nanvuranlat its N-acetyl metabolite, including structural insights into their...
Abstract LAT1 (SLC7A5) transports large neutral amino acids and plays pivotal roles in cancer proliferation, immune response drug delivery. Despite recent advances structural understanding of LAT1, how it discriminates substrates inhibitors including the clinically relevant drugs remains elusive. Here we report six structures across three conformations with bound ligands, elucidating its substrate transport inhibitory mechanisms. JPH203 (also known as nanvuranlat or KYT-0353), an anticancer...
3-(18)F-l-α-methyl-tyrosine ([18F]FAMT), a PET probe for tumor imaging, has advantages of high cancer-specificity and lower physiologic background. FAMT-PET been proved useful in clinical studies the prediction prognosis, assessment therapy response differentiation malignant tumors from inflammation benign lesions. The uptake [18F]FAMT is strongly correlated with expression L-type amino acid transporter 1 (LAT1), an isoform system L upregulated cancers. In this study, to assess...
Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous tissues. Combination therapies cytotoxic with molecularly targeted been pursued to solve fundamental problems. Nanvuranlat (JPH203 or KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), has novel mechanisms action suppress cell proliferation tumor growth...
Background The cytokines TNF (TNFSF2) and IFNγ are important mediators of inflammatory bowel diseases contribute to enhanced intestinal epithelial permeability by stimulating apoptosis and/or disrupting tight junctions. Apoptosis junctions also for tissue morphogenesis, but the effect on process morphogenesis is unknown. Methods/Principal Findings We have employed a three-dimensional cell culture system, reproducing in vivo-like multicellular organization cells, study permeability. show that...