Yamaguchi T

References (24)

Title : Functional roles and localization of hydrolases in the Japanese mitten crab Eriocheir japonica - Takahashi_2023_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_270_110932
Author(s) : Takahashi M , Takahashi K , Yamaguchi T , Kohama T , Hosokawa M
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 270 :110932 , 2023
Abstract : The Japanese mitten crab Eriocheir japonica inhabits rivers throughout Japan and is being cultivated for food. To conduct aquaculture efficiently, it is crucial to comprehend the physiological functions of the target organisms. However, there is a lack of fundamental information on Japanese mitten crabs. In this study, hydrolases were extracted from the midgut glands of Japanese mitten crabs and their metabolic activities were analyzed. An enzyme with hydrolytic activity was discovered within the cytosol of the midgut gland. Western blot analysis also revealed that the Japanese mitten crab contains a hydrolase with cross-reactivity to human carboxylesterase 1 (hCES1) antibodies. The substrate specificity of the S9 fraction of the midgut gland was investigated and, interestingly, it was revealed that it reacts well with indomethacin phenyl ester and fluorescein diacetate, which are substrates of hCES2, not substrates of hCES1. Furthermore, this enzyme was observed to metabolize the ester derivative of astaxanthin, which is a red pigment inherent to the Japanese mitten crab. These findings underscore the significance the midgut gland in the Japanese mitten crab as an important organ for metabolizing both endogenous and exogenous ester-type compounds.
ESTHER : Takahashi_2023_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_270_110932
PubMedSearch : Takahashi_2023_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_270_110932
PubMedID: 38097062

Title : Characterization of a novel hydroxynitrile lyase from Nandina domestica Thunb - Isobe_2018_Biosci.Biotechnol.Biochem_82_1760
Author(s) : Isobe K , Kitagawa A , Kanamori K , Kashiwagi N , Matsui D , Yamaguchi T , Fuhshuku KI , Semba H , Asano Y
Ref : Biosci Biotechnol Biochem , 82 :1760 , 2018
Abstract : The leaves of Nandina domestica Thunb. exhibited high hydroxynitrile lyase (HNL) activity in (R)-mandelonitrile synthesis. The specific activity of young leaves was significantly higher than that of mature leaves. We isolated two HNLs with molecular mass of 24.9 kDa (NdHNL-S) and 28.0 kDa (NdHNL-L) from the young leaves. Both NdHNLs were composed of two identical subunits, without FAD and carbohydrates. We purified NdHNL-L and revealed its enzymatic properties. The whole deduced amino acid sequence of NdHNL-L was not homologous to any other HNLs, and the specific activity for mandelonitrile synthesis by NdHNL-L was higher than that by other plant HNLs. The enzyme catalyzed enantioselective synthesis of (R)-cyanohydrins, exhibited high activity at pH 4.0, and high stability in the pH range of 3.5-8.0 and below 55 degrees C. Thus, NdHNL-L is a novel HNL with novel amino acid sequence and has a potential for the efficient production of (R)-cyanohydrins.
ESTHER : Isobe_2018_Biosci.Biotechnol.Biochem_82_1760
PubMedSearch : Isobe_2018_Biosci.Biotechnol.Biochem_82_1760
PubMedID: 29975178

Title : Hydroxynitrile lyases from cyanogenic millipedes: molecular cloning, heterologous expression, and whole-cell biocatalysis for the production of (R)-mandelonitrile - Yamaguchi_2018_Sci.Rep_8_3051
Author(s) : Yamaguchi T , Nuylert A , Ina A , Tanabe T , Asano Y
Ref : Sci Rep , 8 :3051 , 2018
Abstract : Hydroxynitrile lyases (HNLs), which are key enzymes in cyanogenesis, catalyze the cleavage of cyanohydrins into carbonyl compounds and hydrogen cyanide. Since HNLs also catalyze the reverse reaction, they are used industrially for the asymmetric synthesis of cyanohydrins, which are valuable building blocks of pharmaceuticals and fine chemicals. HNLs have been isolated from cyanogenic plants and bacteria. Recently, an HNL from the cyanogenic millipede Chamberlinius hualienensis was shown to have the highest specific activity for (R)-mandelonitrile synthesis, along with high stability and enantioselectivity. However, no HNLs have been isolated from other cyanogenic millipedes. We identified and characterized HNLs from 10 cyanogenic millipedes in the Paradoxosomatidae and Xystodesmidae. Sequence analyses showed that HNLs are conserved among cyanogenic millipedes and likely evolved from one ancestral gene. The HNL from Parafontaria tonominea was expressed in Escherichia coli SHuffle T7 and showed high specific activity for (R)-mandelonitrile synthesis and stability at a range of pHs and temperatures. The stability of millipede HNLs is likely due to disulfide bond(s). The E. coli cells expressing HNL produced (R)-mandelonitrile with 97.6% enantiomeric excess without organic solvents. These results demonstrate that cyanogenic millipedes are a valuable source of HNLs with high specific activity and stability.
ESTHER : Yamaguchi_2018_Sci.Rep_8_3051
PubMedSearch : Yamaguchi_2018_Sci.Rep_8_3051
PubMedID: 29445093

Title : Distribution of acotiamide, an orally active acetylcholinesterase inhibitor, into the myenteric plexus of rat and dog stomachs - Yoshii_2016_Life.Sci_145_93
Author(s) : Yoshii K , Yamaguchi T , Hirayama M , Toda R , Kinomoto T , Kawabata Y , Chiba K
Ref : Life Sciences , 145 :93 , 2016
Abstract : AIMS: Acotiamide is the first-in-class drug for the treatment of functional dyspepsia. Although pharmacological and therapeutic actions of acotiamide are thought to be derived from its inhibitory effects on acetylcholinesterase (AChE), whether the concentration of acotiamide at the site of action is sufficient to inhibit AChE remains unclear. Since major site of acotiamide action is thought to be the cholinergic nerve terminals in gastric myenteric plexus, we studied the distribution of [(14)C]acotiamide into gastric myenteric plexus. MAIN
METHODS: Distribution of [(14)C]acotiamide was evaluated using macro- and micro-autoradiography in rats and dogs. KEY FINDINGS: The results of macro-autoradiography showed the concentration of radioactivity was 27.9muM in rat stomach, which was 12 times higher than IC50 of acotiamide for rat AChE. Being different from rats, the distribution of radioactivity in the muscular layer was distinguishable from that in the mucosal layer in dog stomach. The concentration of radioactivity in the muscular layer of dog stomach (1.41muM) was approximately two-times lower than those in the mucosal layer, however, it was approximately 1.2 times higher than IC50 of acotiamide for dog AChE. The results of micro-autoradiography also showed the radioactivity distributed homogenously in the muscular layer of rat stomach, suggesting the concentration of radioactivity around the ganglion of myenteric plexus is similar to that in the muscular layer of stomach. SIGNIFICANCE: These findings suggest acotiamide distributes to the myenteric plexus of stomach, a putative site of acotiamide action, with adequate concentrations to inhibit AChE, in both of rat and dog stomachs.
ESTHER : Yoshii_2016_Life.Sci_145_93
PubMedSearch : Yoshii_2016_Life.Sci_145_93
PubMedID: 26682939

Title : Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms - Suzuki_2016_Intern.Med_55_1131
Author(s) : Suzuki T , Sawada S , Ishigaki Y , Tsukita S , Kodama S , Sugisawa T , Imai J , Yamada T , Yamaguchi T , Murano T , Katagiri H
Ref : Intern Med , 55 :1131 , 2016
Abstract : Lipoprotein lipase (LPL) deficiency is a rare monogenic disorder that manifests as severe hypertriglyceridemia. Whether or not LPL deficiency accelerates the development of atherosclerosis remains controversial. We herein report a 66-year-old woman who was homozygous for the R243H LPL mutation. She had developed multiple arterial aneurysms and systemic atherosclerosis despite good control of other atherogenic risk factors, including diabetes. Furthermore, although intensive pharmaceutical therapies had been minimally effective, medium chain triglyceride (MCT) therapy reduced the serum triglyceride levels. Thus, this case suggests important role that mutated LPL protein plays in the progression of atherosclerosis and that MCT therapy is potentially effective, even for severe hypertriglyceridemia due to LPL deficiency.
ESTHER : Suzuki_2016_Intern.Med_55_1131
PubMedSearch : Suzuki_2016_Intern.Med_55_1131
PubMedID: 27150867

Title : Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening - Amano_2015_Bioorg.Med.Chem_23_2310
Author(s) : Amano Y , Tanabe E , Yamaguchi T
Ref : Bioorganic & Medicinal Chemistry , : , 2015
Abstract : Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal structures of these hits were determined via individual soaking. Based on the binding mode, N-ethylmethylamine was identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold were selected from an in-house chemical library and assayed. Although the starting fragment had a weak inhibitory activity (IC50: 800muM), we identified potent inhibitors including 2-({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory activity (IC50: 0.51muM). This corresponded to a more than 1500-fold increase in inhibitory activity compared to the starting fragment. Co-crystal structures of the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic residues is similar to that of the starting fragment. We therefore consider crystallographic fragment screening to be appropriate for the identification of weak but promising fragment hits.
ESTHER : Amano_2015_Bioorg.Med.Chem_23_2310
PubMedSearch : Amano_2015_Bioorg.Med.Chem_23_2310
PubMedID: 25862210
Gene_locus related to this paper: human-EPHX2

Title : Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography - Amano_2014_Bioorg.Med.Chem_22_2427
Author(s) : Amano Y , Yamaguchi T , Tanabe E
Ref : Bioorganic & Medicinal Chemistry , 22 :2427 , 2014
Abstract : Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.
ESTHER : Amano_2014_Bioorg.Med.Chem_22_2427
PubMedSearch : Amano_2014_Bioorg.Med.Chem_22_2427
PubMedID: 24656800
Gene_locus related to this paper: human-EPHX2

Title : Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein - Wang_2011_J.Biol.Chem_286_15707
Author(s) : Wang H , Bell M , Sreenivasan U , Hu H , Liu J , Dalen K , Londos C , Yamaguchi T , Rizzo MA , Coleman R , Gong D , Brasaemle D , Sztalryd C
Ref : Journal of Biological Chemistry , 286 :15707 , 2011
Abstract : Lipolysis is a critical metabolic pathway contributing to energy homeostasis through degradation of triacylglycerides stored in lipid droplets (LDs), releasing fatty acids. Neutral lipid lipases act at the oil/water interface. In mammalian cells, LD surfaces are coated with one or more members of the perilipin protein family, which serve important functions in regulating lipolysis. We investigated mechanisms by which three perilipin proteins control lipolysis by adipocyte triglyceride lipase (ATGL), a key lipase in adipocytes and non-adipose cells. Using a cell culture model, we examined interactions of ATGL and its co-lipase CGI-58 with perilipin 1 (perilipin A), perilipin 2 (adipose differentiation-related protein), and perilipin 5 (LSDP5) using multiple techniques as follows: anisotropy Forster resonance energy transfer, co-immunoprecipitation, [(32)P]orthophosphate radiolabeling, and measurement of lipolysis. The results show that ATGL interacts with CGI-58 and perilipin 5; the latter is selectively expressed in oxidative tissues. Both proteins independently recruited ATGL to the LD surface, but with opposite effects; interaction of ATGL with CGI-58 increased lipolysis, whereas interaction of ATGL with perilipin 5 decreased lipolysis. In contrast, neither perilipin 1 nor 2 interacted directly with ATGL. Activation of protein kinase A (PKA) increased [(32)P]orthophosphate incorporation into perilipin 5 by 2-fold, whereas neither ATGL nor CGI-58 was labeled under the incubation conditions. Cells expressing both ectopic perilipin 5 and ATGL showed a 3-fold increase in lipolysis following activation of PKA. Our studies establish perilipin 5 as a novel ATGL partner and provide evidence that the protein composition of perilipins at the LD surface regulates lipolytic activity of ATGL.
ESTHER : Wang_2011_J.Biol.Chem_286_15707
PubMedSearch : Wang_2011_J.Biol.Chem_286_15707
PubMedID: 21393244

Title : Crucial role of CGI-58\/alpha\/beta hydrolase domain-containing protein 5 in lipid metabolism - Yamaguchi_2010_Biol.Pharm.Bull_33_342
Author(s) : Yamaguchi T
Ref : Biol Pharm Bull , 33 :342 , 2010
Abstract : The surfaces of lipid droplets (LDs) constitute major sites of regulated accumulation and degradation of lipid in cells, and hence play important roles in lipid homeostasis of the whole body. CGI-58 (also called alpha/beta hydrolase domain-containing protein 5 (ABHD5)) is a member of the alpha/beta-hydrolase family of proteins and is a product of the causal gene of Chanarin-Dorfman syndrome (CDS), which is characterized by excessive storage of triacylglycerol (TG) in various tissues. CGI-58 is distributed predominantly on the surface of LDs and plays a crucial role in TG degradation in cells. In the process of lipolysis, CGI-58 coordinates with several proteins, including perilipin, a member of the PAT family of proteins, and adipose triglyceride lipase (ATGL), a putative rate-limiting enzyme for TG degradation in adipocytes. Besides its role in adipocytes, CGI-58 is involved in lipid degradation in various tissues, including those of skin and liver. This review focuses on the functions and protein interactions of CGI-58 on the surface of LDs in the regulation of fat mobilization in cells.
ESTHER : Yamaguchi_2010_Biol.Pharm.Bull_33_342
PubMedSearch : Yamaguchi_2010_Biol.Pharm.Bull_33_342
PubMedID: 20190389

Title : Immobilization of Pseudomonas cepacia lipase onto electrospun polyacrylonitrile fibers through physical adsorption and application to transesterification in nonaqueous solvent - Sakai_2010_Biotechnol.Lett_32_1059
Author(s) : Sakai S , Liu Y , Yamaguchi T , Watanabe R , Kawabe M , Kawakami K
Ref : Biotechnol Lett , 32 :1059 , 2010
Abstract : The lipase of Pseudomonas cepacia was immobilized onto electrospun polyacrylonitrile (PAN) fibers and used for the conversion of (S)-glycidol with vinyl n-butyrate to glycidyl n-butyrate in isooctane. The rate of reaction with the adsorbed lipase was 23-fold higher than the initial material. After 10 recyclings, the initial reaction rate was 80% of the original rate. This system of enzyme immobilization is therefore suitable for carrying out transesterification reactions in nonaqueous solvents.
ESTHER : Sakai_2010_Biotechnol.Lett_32_1059
PubMedSearch : Sakai_2010_Biotechnol.Lett_32_1059
PubMedID: 20424890

Title : Production of butyl-biodiesel using lipase physically-adsorbed onto electrospun polyacrylonitrile fibers - Sakai_2010_Bioresour.Technol_101_7344
Author(s) : Sakai S , Liu Y , Yamaguchi T , Watanabe R , Kawabe M , Kawakami K
Ref : Bioresour Technol , 101 :7344 , 2010
Abstract : Butyl-biodiesel production using electrospun polyacrylonitrile fibers with Pseudomonas cepacia lipase immobilized through physical adsorption was studied. About 80% conversion to butyl-biodiesel was achieved after 24h by suspending the catalyst at 2.4 mg/mL in a mixture of rapeseed oil and n-butanol at a molar ratio of 1:3, containing water at 8000 ppm at 40 degrees C. A further 24h of operation resulted in 94% conversion. The initial reaction rate detected for this process was 65-fold faster than those detected for Novozym 435 on a total catalyst mass basis. The immobilized lipase continued to work as a catalyst for 27 d, within a 15% reduction in conversion yield at the outlet of the reactor compared with the average value detected during the first 3d of operation in a continuous butyl-biodiesel production system.
ESTHER : Sakai_2010_Bioresour.Technol_101_7344
PubMedSearch : Sakai_2010_Bioresour.Technol_101_7344
PubMedID: 20493682

Title : Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins - Wang_2009_J.Biol.Chem_284_32116
Author(s) : Wang H , Hu L , Dalen K , Dorward H , Marcinkiewicz A , Russell D , Gong D , Londos C , Yamaguchi T , Holm C , Rizzo MA , Brasaemle D , Sztalryd C
Ref : Journal of Biological Chemistry , 284 :32116 , 2009
Abstract : Lipolysis is an important metabolic pathway controlling energy homeostasis through degradation of triglycerides stored in lipid droplets and release of fatty acids. Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells. We applied fluorescence microscopic tools to analyze proteins in situ in cultured Chinese hamster ovary cells using fluorescence recovery after photobleaching and anisotropy Forster resonance energy transfer. Fluorescence recovery after photobleaching data show that ADFP and LSDP5 exchange between lipid droplet and cytoplasmic pools, whereas perilipin A does not. Differences in protein mobility do not correlate with PAT protein-mediated control of lipolysis catalyzed by HSL or endogenous lipases. Forster resonance energy transfer and co-immunoprecipitation experiments reveal that each of the three PAT proteins bind HSL through interaction of the lipase with amino acids within the highly conserved amino-terminal PAT-1 domain. ADFP and LSDP5 bind HSL under basal conditions, whereas phosphorylation of serine residues within three amino-terminal protein kinase A consensus sequences of perilipin A is required for HSL binding and maximal lipolysis. Finally, protein kinase A-mediated phosphorylation of HSL increases lipolysis in cells expressing ADFP or LSDP5; in contrast, phosphorylation of perilipin A exerts the major control over HSL-mediated lipolysis when perilipin is the main lipid droplet protein.
ESTHER : Wang_2009_J.Biol.Chem_284_32116
PubMedSearch : Wang_2009_J.Biol.Chem_284_32116
PubMedID: 19717842

Title : Chanarin-Dorfman syndrome: deficiency in CGI-58, a lipid droplet-bound coactivator of lipase - Yamaguchi_2009_Biochim.Biophys.Acta_1791_519
Author(s) : Yamaguchi T , Osumi T
Ref : Biochimica & Biophysica Acta , 1791 :519 , 2009
Abstract : Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disease of lipid metabolism; it is associated with congenital ichthyosis typed as non-bullous congenital ichthyosiform erythroderma (NCIE). CDS is characterized by the presence of an abnormally large number of cytosolic lipid droplets containing triacylglycerol (TG) in various tissues such as the skin, liver, and leukocytes. Mutations in the CGI-58 (also called ABHD5) gene encoding a 39-kDa protein of the alpha/beta hydrolase domain subfamily have been shown to be responsible for this disorder. In adipocytes, CGI-58 is involved in TG degradation on lipid droplets; in doing so, it coordinates with several lipolytic factors including perilipin, a member of the PAT protein family, and ATGL, a putative rate-limiting lipase in adipocytes. In quiescent adipocytes, CGI-58 interacts with perilipin on the surfaces of lipid droplets. Upon hormonal stimulation, CGI-58 facilitates massive lipolysis by activating ATGL. Some CGI-58 mutations found in CDS patients cancel the ability to interact with perilipin or activate ATGL, indicating that the loss of these interactions is physiologically important. However, based on the tissue distributions of these lipolytic factors, there are likely multiple molecular targets of CGI-58 actions. This in turn gives rise to the multiple phenotypes of CDS, such as ichthyosis, liver steatosis, or neurosensory diseases.
ESTHER : Yamaguchi_2009_Biochim.Biophys.Acta_1791_519
PubMedSearch : Yamaguchi_2009_Biochim.Biophys.Acta_1791_519
PubMedID: 19061969
Gene_locus related to this paper: human-ABHD5

Title : Transesterification by lipase entrapped in electrospun poly(vinyl alcohol) fibers and its application to a flow-through reactor - Sakai_2008_J.Biosci.Bioeng_105_687
Author(s) : Sakai S , Antoku K , Yamaguchi T , Kawakami K
Ref : J Biosci Bioeng , 105 :687 , 2008
Abstract : We entrapped lipase in electrospun poly(vinyl alcohol) fibers of approximately 1 mum in diameter and evaluated the transesterification activity by converting (s)-glycidol to glycidyl n-butyrate with vinyl n-butyrate. The initial transesterification rate of the entrapped lipase was 5.2-fold faster than that of non-treated lipase. The fibrous membrane could be used as a component of a flow-through reactor for continuous transesterification.
ESTHER : Sakai_2008_J.Biosci.Bioeng_105_687
PubMedSearch : Sakai_2008_J.Biosci.Bioeng_105_687
PubMedID: 18640613

Title : CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation - Yamaguchi_2007_J.Lipid.Res_48_1078
Author(s) : Yamaguchi T , Omatsu N , Morimoto E , Nakashima H , Ueno K , Tanaka T , Satouchi K , Hirose F , Osumi T
Ref : J Lipid Res , 48 :1078 , 2007
Abstract : A lipid droplet (LD)-associated protein, perilipin, is a critical regulator of lipolysis in adipocytes. We previously showed that Comparative Gene Identification-58 (CGI-58), a product of the causal gene of Chanarin-Dorfman syndrome, interacts with perilipin on LDs. In this study, we investigated the function of CGI-58 using RNA interference. Notably, CGI-58 knockdown caused an abnormal accumulation of LDs in both 3T3-L1 preadipocytes and Hepa1 hepatoma cells. CGI-58 knockdown did not influence the differentiation of 3T3-L1 adipocytes but reduced the activity of both basal and cAMP-dependent protein kinase-stimulated lipolysis. In vitro studies showed that CGI-58 itself does not have lipase/esterase activity, but it enhanced the activity of adipose triglyceride lipase. Upon lipolytic stimulation, endogenous CGI-58 was rapidly dispersed from LDs into the cytosol along with small particulate structures. This shift in localization depends on the phosphorylation of perilipin, because phosphorylated perilipin lost the ability to bind CGI-58. During lipolytic activation, LDs in adipocytes vesiculate into micro-LDs. Using coherent anti-Stokes Raman scattering microscopy, we pursued the formation of micro-LDs in single cells, which seemed to occur in cytoplasmic regions distant from the large central LDs. CGI-58 is not required for this process. Thus, CGI-58 facilitates lipolysis in cooperation with perilipin and other factors, including lipases.
ESTHER : Yamaguchi_2007_J.Lipid.Res_48_1078
PubMedSearch : Yamaguchi_2007_J.Lipid.Res_48_1078
PubMedID: 17308334

Title : Analysis of interaction partners for perilipin and ADRP on lipid droplets - Yamaguchi_2006_Mol.Cell.Biochem_284_167
Author(s) : Yamaguchi T , Omatsu N , Omukae A , Osumi T
Ref : Molecular & Cellular Biochemistry , 284 :167 , 2006
Abstract : Despite the critical roles of intracellular lipid droplets (LDs) in lipid storage and metabolism, little is known about the molecular mechanisms of their functions. Several protein components associated with the surface of LDs have been identified. A major one is perilipin in adipocytes and steroidogenic cells, whereas ADRP in most other cell types. They are loosely grouped as a small protein family sharing a common N-terminal motif, called the PAT domain. Perilipin regulates the breakdown of triacylglycerol in LDs via its phosphorylation. ADRP is characterized as a fatty acid binding protein and involved in lipid uptake and LD formation. For examining the functions of perilipin and ADRP at the molecular level, we performed yeast two-hybrid screening in this study, to find their functional partners. We identified CGI-58, a product of the causal gene of Chanarin-Dorfman syndrome (CDS), as an interactor for both perilipin and ADRP. Specific interaction between CGI-58 and perilipin was confirmed in a GST-pulldown assay and supported by fluorescence microscopic analyses. We further demonstrated that CGI-58 is principally located at the surface of LDs in 3T3-L1 cells, together with perilipin, and its expression is upregulated upon stimulation for adipocyte differentiation. Other than CGI-58, we also identified in yeast two-hybrid screening HSP86 and D52 tumor proteins as binding partners of perilipin, and IRG-47 of ADRP. These factors might be cooperated with perilipin and ADRP, and hence involved in membrane dynamics of LDs as well as the regulation of lipolysis on the surface of LDs.
ESTHER : Yamaguchi_2006_Mol.Cell.Biochem_284_167
PubMedSearch : Yamaguchi_2006_Mol.Cell.Biochem_284_167
PubMedID: 16532261

Title : Teratogenicity and developmental toxicity of chlorpyrifos. Maternal exposure during organogenesis in mice - Tian_2005_Reprod.Toxicol_20_267
Author(s) : Tian Y , Ishikawa H , Yamaguchi T , Yamauchi T , Yokoyama K
Ref : Reprod Toxicol , 20 :267 , 2005
Abstract : Chlorpyrifos, an organophosphate pesticide, was evaluated for potential teratogenicity and developmental toxicity in mice. Pregnant females were given a single intraperitoneal injection (40 or 80 mg/kg) on day 10 of gestation and fetuses were evaluated on gestation day 17. At 80 mg/kg, chlorpyrifos treatment resulted in a significant reduction in numbers of live fetuses, and increase in resorptions, versus control litters. There was no indication of maternal toxicity. External and skeletal malformations were observed at 80 mg/kg, but not 40 mg/kg. Rates of fetuses with cleft palate increased significantly (p<0.05) following 80 mg/kg chlorpyrifos (5.97%) versus control litters (0.97%). Similarly, the absence of thoracic vertebrae was increased and the number of caudal vertebrae was significantly decreased. It is suggested that chlorpyrifos is teratogenic and embryotoxic in mice at doses below those that cause significant maternal toxicity.
ESTHER : Tian_2005_Reprod.Toxicol_20_267
PubMedSearch : Tian_2005_Reprod.Toxicol_20_267
PubMedID: 15907662

Title : Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons - Kume_2005_Eur.J.Pharmacol_527_77
Author(s) : Kume T , Sugimoto M , Takada Y , Yamaguchi T , Yonezawa A , Katsuki H , Sugimoto H , Akaike A
Ref : European Journal of Pharmacology , 527 :77 , 2005
Abstract : We previously reported that donepezil, a central-type acetylcholinesterase inhibitor, showed neuroprotective action via alpha4-and alpha7-nicotinic acetylcholine receptors against glutamate neurotoxicity in rat cortical culture. The present study was performed to investigate whether the neuroprotective action of acetylcholinesterase inhibitors is accompanied by the alteration of expression and function of nicotinic receptors. Four days treatment with acetylcholinesterase inhibitors (10 microM) enhanced the nicotine-induced increase of the intracellular calcium concentration. Immunoblot analysis revealed that donepezil increased both alpha4 and alpha7 subunit proteins. Donepezil and galanthamine increased the number of cells expressing alpha4- and alpha7-nicotinic receptors in immunocytochemical analysis. We examined whether up-regulation of nicotinic receptors affected the neuroprotective action of acetylcholinesterase inhibitors. Under up-regulating conditions, donepezil and galanthamine exerted neuroprotective action at lower concentrations. These results suggest that donepezil and galanthamine up-regulate nicotinic receptors in cortical neurons, and that the up-regulation of nicotinic receptors may make cortical neurons more sensitive to the neuroprotective action of donepezil and galanthamine.
ESTHER : Kume_2005_Eur.J.Pharmacol_527_77
PubMedSearch : Kume_2005_Eur.J.Pharmacol_527_77
PubMedID: 16313899

Title : CGI-58 interacts with perilipin and is localized to lipid droplets. Possible involvement of CGI-58 mislocalization in Chanarin-Dorfman syndrome - Yamaguchi_2004_J.Biol.Chem_279_30490
Author(s) : Yamaguchi T , Omatsu N , Matsushita S , Osumi T
Ref : Journal of Biological Chemistry , 279 :30490 , 2004
Abstract : Lipid droplets (LDs) are a class of ubiquitous cellular organelles that are involved in lipid storage and metabolism. Although the mechanisms of the biogenesis of LDs are still unclear, a set of proteins called the PAT domain family have been characterized as factors associating with LDs. Perilipin, a member of this family, is expressed exclusively in the adipose tissue and regulates the breakdown of triacylglycerol in LDs via its phosphorylation. In this study, we used a yeast two-hybrid system to examine the potential function of perilipin. We found direct interaction between perilipin and CGI-58, a deficiency of which correlated with the pathogenesis of Chanarin-Dorfman syndrome (CDS). Endogenous CGI-58 was distributed predominantly on the surface of LDs in differentiated 3T3-L1 cells, and its expression increased during adipocyte differentiation. Overexpressed CGI-58 tagged with GFP gathered at the surface of LDs and colocalized with perilipin. This interaction seems physiologically important because CGI-58 mutants carrying an amino acid substitution identical to that found in CDS lost the ability to be recruited to LDs. These mutations significantly weakened the binding of CGI-58 with perilipin, indicating that the loss of this interaction is involved in the etiology of CDS. Furthermore, we identified CGI-58 as a binding partner of ADRP, another PAT domain protein expressed ubiquitously, by yeast two-hybrid assay. GFP-CGI-58 expressed in non-differentiated 3T3-L1 or CHO-K1 cells was colocalized with ADRP, and the CGI-58 mutants were not recruited to LDs carrying ADRP, indicating that CGI-58 may also cooperate with ADRP.
ESTHER : Yamaguchi_2004_J.Biol.Chem_279_30490
PubMedSearch : Yamaguchi_2004_J.Biol.Chem_279_30490
PubMedID: 15136565
Gene_locus related to this paper: ratno-abhd5 , human-ABHD5

Title : Sarin poisoning on Tokyo subway - Ohbu_1997_South.Med.J_90_587
Author(s) : Ohbu S , Yamashina A , Takasu N , Yamaguchi T , Murai T , Nakano K , Matsui Y , Mikami R , Sakurai K , Hinohara S
Ref : South Med J , 90 :587 , 1997
Abstract : On the day of the disaster, 641 victims were seen at St. Luke's International Hospital. Among those, five victims arrived with cardiopulmonary or respiratory arrest with marked miosis and extremely low serum cholinesterase values; two died and three recovered completely. In addition to these five critical patients, 106 patients, including four pregnant women, were hospitalized with symptoms of mild to moderate exposure. Other victims had only mild symptoms and were released after 6 hours of observation. Major signs and symptoms in victims were miosis, headache, dyspnea, nausea, ocular pain, blurred vision, vomiting, coughing, muscle weakness, and agitation. Almost all patients showed miosis and related symptoms such as headache, blurred vision, or visual darkness. Although these physical signs and symptoms disappeared within a few weeks, psychologic problems associated with posttraumatic stress disorder persisted longer. Also, secondary contamination of the house staff occurred, with some sort of physical abnormality in more than 20%.
ESTHER : Ohbu_1997_South.Med.J_90_587
PubMedSearch : Ohbu_1997_South.Med.J_90_587
PubMedID: 9191733

Title : Effects of (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate (YM796), a novel muscarinic agonist, on disturbance of passive avoidance learning behavior in drug-treated and senescence-accelerated mice - Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
Author(s) : Suzuki M , Yamaguchi T , Ozawa Y , Ohyama M , Yamamoto M
Ref : Journal of Pharmacology & Experimental Therapeutics , 275 :728 , 1995
Abstract : Effects of YM796 (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate; a novel muscarinic agonist, were observed on disturbance of passive avoidance learning behavior in drug- (protein synthesis inhibitor and anticholinergic drugs) treated and senescence-accelerated mice in comparison with those of a muscarinic agonist (AF102B) and acetylcholinesterase inhibitors (E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanone-2-yl) methyl] piperidene hydrochloride), NIK247 [9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate hydrochloride], THA (9-amino-1,2,3,4-tetrahydroacridine) and physostigmine). All tested drugs administered before training significantly prolonged the shortened latency of step-through induced by the protein synthesis inhibitor cycloheximide (150 mg/kg s.c.). This shortened latency was also significantly prolonged when YM796 was administered immediately after training, but not when administered before the test trial. The ameliorating effect of YM796 on the impairment in learning behavior by cycloheximide was significantly suppressed by pirenzepine (0.1 micrograms/mouse i.c.v.). When administered before training, all test drugs prolonged the shortened latency of step-through induced by treatment with the anticholinergic drugs [scopolamine (1 mg/kg s.c.) and hemicholinium-3 (0.3 microgram/mouse i.c.v.)], suggesting that they ameliorated the impairment of learning behavior. This shortened latency in scopolamine-treated mice was also significantly prolonged by YM796, AF102B, E2020, NIK247 and physostigmine when administered immediately after training, but not when administered before the test trial. The pharmacological actions of YM796 administered immediately after training and before the test trial in hemicholinium-3-treated mice were similar to those in scopolamine-treated mice.
ESTHER : Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
PubMedSearch : Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
PubMedID: 7473160

Title : Effect of YM796, a novel muscarinic agonist, on the impairment of passive avoidance response in senescence-accelerated mice - Suzuki_1995_Pharmacol.Biochem.Behav_51_623
Author(s) : Suzuki M , Yamaguchi T , Ozawa Y , Iwai A , Yamamoto M
Ref : Pharmacology, Biochemistry & Behavior , 51 :623 , 1995
Abstract : We compared the effects of YM796 [(-)-S-2,8-dimethyl-3-methylene-1-oxa-8- azaspiro[4,5]-decane L-tartrate monohydrate], a novel muscarinic agonist, on passive avoidance response with those of the cholinomimetics AF102B [(+/-)-cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine hydrochloride] and NIK247 [9-amino-2,3,5,6,7,8-hexahydro1H-cyclopenta(b)- quinoline monohydrate hydrochloride] in senescence-accelerated mice. SAMP8@YAN (SAM-P/8, senescence-accelerated-prone substrain) showed an age-dependent shortening in the latency of step-through when compared with SAMR1/YAN (SAM-R/1, senescence-accelerated-resistant substrain). The shortened latency of step-through in SAMP8@YAN was prolonged by administration of YM796 (0.3 and 1 mg/kg, PO), AF102B (3 and 10 mg/kg PO), and NIK247 (30 mg/kg, PO) in a bell-shaped manner. In contrast, amitriptyline (10, 30, and 50 mg/kg, PO), with cholinolytic properties, had no effect on this shortened latency of step-through. These results suggest that YM796, AF102B, and NIK247 ameliorated the disturbance of learning behavior, presumably due to facilitation of the central cholinergic system in SAMP8@YAN mice and that SAMP8@YAN may be an appropriate age-dependent model of amnesia for evaluating pharmacological actions of drugs.
ESTHER : Suzuki_1995_Pharmacol.Biochem.Behav_51_623
PubMedSearch : Suzuki_1995_Pharmacol.Biochem.Behav_51_623
PubMedID: 7675834

Title : Purification and characterization of hamster hepatic microsomal N,O-acetyltransferase - Sone_1992_Chem.Pharm.Bull.(Tokyo)_40_2857
Author(s) : Sone T , Yamaguchi T , Isobe M , Takabatake E , Adachi T , Hirano K , Wang CY
Ref : Chem Pharm Bull (Tokyo) , 40 :2857 , 1992
Abstract : A microsomal N,O-acetyltransferase which activates carcinogenic arylacetohydroxamic acids was purified 75-fold from hamster liver sequentially by anion exchange column chromatography, chromatofocusing, gel filtration, and hydroxyapatite column chromatography. The purified enzyme, AT-2, was a glycoprotein with a molecular weight of 60000 and a pI value of 5.4. The N-terminal amino acid sequence of AT-2 was: 60000 and a pI value of 5.4. The N-terminal amino acid sequence of AT-2 was: Asp-Ser-Pro-Ser-Pro-Ile-Arg-Asn-Thr-His-Thr-Gly-Gln-Val-Arg-Gly-Leu-Val- His- Lys-. This sequence was highly homologous to that of the form 2 carboxylesterase of rabbit liver, but not to that of major hepatic microsomal carboxylesterases of hamster and other species. AT-2 catalyzed the hydrolysis of 4-nitrophenyl acetate and the N,O-acetyltransfer of N-hydroxy-2-acetylaminofluorene. Both enzyme activities were strongly inhibited by paraoxon, but not by iodoacetamide. These results demonstrate that this N,O-acetyltransferase is a member of carboxylesterase (EC 3.1.1.1).
ESTHER : Sone_1992_Chem.Pharm.Bull.(Tokyo)_40_2857
PubMedSearch : Sone_1992_Chem.Pharm.Bull.(Tokyo)_40_2857
PubMedID: 1464118
Gene_locus related to this paper: mesau-cxest2

Title : A kinetic study of stimulus-induced vesicle recycling in electromotor nerve terminals using labile and stable vesicle markers - Agoston_1986_J.Neurochem_47_1584
Author(s) : Agoston DV , Dowe GH , Fiedler W , Giompres PE , Roed IS , Walker JH , Whittaker VP , Yamaguchi T
Ref : Journal of Neurochemistry , 47 :1584 , 1986
Abstract : The kinetics of recovery, by recycling electromotor synaptic vesicles, of the biophysical parameters of the reserve population has been studied in perfused blocks of electric organ of Torpedo marmorata prestimulated in vivo, followed by density gradient separation of the extracted vesicles in a zonal rotor using labile (acetylcholine and ATP) and stable (proteoglycan) vesicle markers. Stimulation in vivo at 0.15 Hz for 3.3 h depleted tissue acetylcholine much less than stimulation at 1 Hz for 1 h but nevertheless generated a much larger pool of recycled vesicles that recovered more slowly. At the lower rate of stimulation, recovery of the biophysical characteristics of the reserve population by the recycled vesicles, identified by their content of newly synthesized transmitter, was essentially complete by 8 h. The stable proteoglycan marker was immunochemically assayed and was bimodally distributed in the vesicle-containing portion of the density gradient even in experiments with unstimulated or recovered tissue. The second peak corresponded with that of newly synthesized transmitter and was thus identified as containing the recycled vesicles. Its normalized acetylcholine/proteoglycan ratio was lower than that of the first peak, which is consistent with earlier findings that recycled vesicles, before recovery, are only partially loaded with transmitter. However, as expected, the proportion of total vesicular proteoglycan and acetylcholine associated with the recycled vesicle fraction was very much lower in preparations derived from unstimulated or recovered tissue than in those from recently stimulated tissue.
ESTHER : Agoston_1986_J.Neurochem_47_1584
PubMedSearch : Agoston_1986_J.Neurochem_47_1584
PubMedID: 3760875