A5056711785- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Bacterial Genetics and Biotechnology
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Lipid Membrane Structure and Behavior
- Cell death mechanisms and regulation
- Vibrio bacteria research studies
- Glycosylation and Glycoproteins Research
- Polyamine Metabolism and Applications
- Receptor Mechanisms and Signaling
- Inflammatory mediators and NSAID effects
- Endoplasmic Reticulum Stress and Disease
- Amino Acid Enzymes and Metabolism
- Antibiotic Resistance in Bacteria
- Clostridium difficile and Clostridium perfringens research
- Alzheimer's disease research and treatments
- Computational Drug Discovery Methods
- Immune Response and Inflammation
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Infant Nutrition and Health
- Transgenic Plants and Applications
Doshisha University
2015-2025
Saitama International Medical Center
2000-2007
Japan Science and Technology Agency
2004-2006
Nara Medical University
2002
Harvard University
1997-2000
Beth Israel Deaconess Medical Center
1998-2000
Japan Research Institute
2000
Keio University
1991-2000
Takeda (Japan)
1967-1997
Keio University Hospital
1992-1997
Protein kinase C (PKC) family members play significant roles in a variety of intracellular signal transduction processes, but information about the substrate specificities each PKC member is quite limited. In this study, we have determined optimal peptide sequence for nine human isozymes (α, βI, βII, γ, δ, ϵ, η, μ, and ζ) by using an oriented library. All preferentially phosphorylated peptides with hydrophobic amino acids at position +1 carboxyl-terminal Ser basic residues −3. isozymes,...
We studied the mechanism of uptake and metabolism exogenous phospholipids in mouse peritoneal macrophages using vesicles composed various cholesterol. Macrophages culture were found to actively incorporate metabolize phosphatidylcholine/cholesterol containing small amounts acidic such as phosphatidylserine, phosphatidylinositol, or phosphatidic acid store fatty acyl chains cholesterol triacylglycerol cholesteryl ester form their cytosol. These cells exhibited massive oil red O-positive lipid...
Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results fatal systemic complications, such as neurological damage hemolytic-uremic syndrome. Because Stx circulating the blood is a major causative factor of these development neutralizer that functions circulation holds promise viable therapy. Here we developed series carbosilane dendrimers, trisaccharides globotriaosyl ceramide, receptor for Stx, were...
Phosphatidylserine (PS) is a relatively minor constituent of biological membranes. Despite its low abundance, PS in the plasma membrane (PM) plays key roles various phenomena such as coagulation cascade, clearance apoptotic cells, and recruitment signaling molecules. also localizes endocytic organelles, but how this relates to cellular functions remains unknown. Here we report that essential for retrograde traffic at recycling endosomes (REs). was most concentrated REs among intracellular...
Shiga toxin (Stx) is a major virulence factor in infection with Stx-producing Escherichia coli (STEC). We developed series of linear polymers acrylamide, each different density trisaccharide globotriaosylceramide (Gb3), which receptor for Stx, and identified Gb3 highly clustered trisaccharides as Stx adsorbents functioning the gut. The specifically bound to both Stx1 Stx2 high affinity markedly inhibited cytotoxic activities these toxins. Oral administration protected mice after fatal dose...
Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that release nucleoside 5'-monophosphate from a variety of nucleotides and nucleotide derivatives. The mammalian NPP family comprises seven members, but only three these (NPP1-3) have been studied in some detail. Previously we showed lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid, is identical NPP2. More recently an...
The effects of chronic treatment with an angiotensin II receptor antagonist, candesartan cilexetil (TCV-116, 0.1, 1, 10 mg/kg), and converting enzyme inhibitor, enalapril maleate (enalapril, on the development end-organ damage were examined in stroke-prone spontaneously hypertensive rats (SHRSP). control SHRSP developed severe hypertension stroke signs increased urinary protein excretion. TCV-116 (0.1 mg/kg) reduced incidence excretion without affecting blood pressure. (1 pressure,...
Shiga toxin (Stx) is a major virulence factor of Stx-producing Escherichia coli. Recently, we developed therapeutic Stx neutralizer with 6 trisaccharides globotriaosyl ceramide, receptor for Stx, in its dendrimer structure (referred to as "SUPER TWIG [1]6") function the circulation. Here, determined optimal SUPER it circulation and identified 18 trisaccharides, (2)18, another potent neutralizer. TWIGs (1)6 (2)18 shared structural similarity, dumbbell shape which 2 clusters were connected via...
Abstract Inhibition of amyloid-β peptide (Aβ) accumulation in the brain is a promising approach for treatment Alzheimer’s disease (AD). Aβ produced by β-secretase and γ-secretase endosomes via sequential proteolysis amyloid precursor protein (APP). APP have common feature to readily cluster form multimers. Here, using multivalent library screens, we identified tetravalent peptide, LME-tet, which binds interactions. In cells, LME-tet-bound plasma membrane transported endosomes, blocking...
Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7 causes bloody diarrhea and hemorrhagic colitis in humans, sometimes resulting fatal systemic complications. Among the known Stx family members, Stx2 is responsible for most severe forms of disease. binds to target cells via multivalent interactions between its B-subunit pentamer globotriaosyl ceramide. After binding, it first retrogradely transported Golgi then endoplasmic reticulum (ER). Using a peptide library approach, we...
Understanding the substrate recognition mechanism of γ-secretase is a key step for establishing substrate-specific inhibition amyloid β-protein (Aβ) production. However, it widely believed that promiscuous protease and its elusive. Here we show distinguishes ectodomain length substrates preferentially captures cleaves containing short ectodomain. We also subset peptides CDCYCxxxxCxCxSC motif binds to amino terminus C99 inhibits Aβ production in manner. Interestingly, these suppress...
Globotriaosylceramide (Gb3) is a well known receptor for Shiga toxin (Stx), produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae. The expression of Gb3 also affects several diseases, including cancer metastasis Fabry disease, which prompted us to look factors involved in its metabolism. In the present study, we isolated two cDNAs that conferred resistance Stx-induced cell death HeLa cells cloning: ganglioside GM3 synthase COOH terminus region glutamate receptor,...
Yip1A, a mammalian homologue of yeast Yip1p, is multi-spanning membrane protein that considered to be involved in transport between the endoplasmic reticulum (ER) and Golgi. However, precise role Yip1A cells remains unclear. We show here endogenous localized ER-Golgi intermediate compartment (ERGIC). Knockdown by RNAi did not induce morphological changes Golgi, ER, or ERGIC. By analyzing number intracellular pathways, we found knockdown delayed Shiga toxin from Golgi but affect anterograde...
Abstract The tumor-elicited inflammation is closely related to tumor microenvironment during progression. S100A8 , an endogenous ligand of Toll-like receptor 4 (TLR4), known as a key molecule in the and premetastatic niche formation. We firstly generated novel multivalent competitive inhibitory peptide (divalent peptide3A5) against TLR4/MD-2, using alanine scanning. Divalent peptide3A5 suppressed S100A8-mediated interleukin-8 vascular endothelial growth factor production human colorectal...
We previously developed linear polymers bearing clustered trisaccharides of globotriaosylceramide (Gb3) as orally applicable Shiga toxin (Stx) neutralizers. Here, using a Gb3 polymer with short spacer tethering the trisaccharide to core, we found that shortening length markedly reduced binding affinity for Stx2 but not Stx1. Moreover, mutational analysis revealed essential sites terminal were completely different between Stx1 and Stx2. These results provide molecular basis interaction Stx B...
ABSTRACT Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which causes gastrointestinal diseases and sometimes fatal systemic complications. Recently, we developed an oral Stx2 inhibitor known as Ac-PPP-tet that exhibits remarkable therapeutic potency STEC infection model. However, the precise mechanism underlying vivo effects of unknown. Here, found completely inhibited fluid accumulation rabbit ileum caused by direct injection Stx2....
Tricellular tight junctions (t TJ s) are specialized structural variants of within tricellular contacts an epithelial sheet and comprise several transmembrane proteins including lipolysis‐stimulated lipoprotein receptor (angulin‐1/LSR) tricellulin. To elucidate the mechanism its formation, we carried out stepwise screening kinase inhibitors followed by RNA i to identify kinases that regulate intracellular localization angulin‐1/ LSR tTJs using a fluorescence image‐based screen. We found...
ABSTRACT Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic Escherichia coli that occasionally causes fatal systemic complications. We recently developed tetravalent peptide (PPP-tet) neutralizes the cytotoxicity Stx2 using multivalent library approach. In this study, we used technique to identify series peptides bound Stx1, another Stx family member, with high affinity by targeting one receptor-binding site B subunit. One peptide, MMA-tet, markedly inhibited Stx1 and greater...