Tomita T

References (26)

Title : Common substitution mutation F348Y of acetylcholinesterase gene contributes to organophosphate and carbamate resistance in Cimex lectularius and C. hemipterus - Komagata_2021_Insect.Biochem.Mol.Biol__103637
Author(s) : Komagata O , Kasai S , Itokawa K , Minagawa K , Kazuma T , Mizutani K , Muto A , Tanikawa T , Adachi M , Komatsu N , Tomita T
Ref : Insect Biochemistry & Molecular Biology , :103637 , 2021
Abstract : Bed bug control highly depends on insecticides with a limited number of modes of action, especially since the global prevalence of pyrethroid resistance. De facto insecticide options against bed bugs in Japan are acetylcholinesterase inhibitors (AChEis) that consist of organophosphates and carbamates. However, the status of AChEi resistance and the mechanisms involved have not been ascertained. An amino acid substitution mutation, F348Y (or F331Y in standard numbering), occurring at an acyl-binding site of the paralogous AChE gene (p-Ace), was identified among AChEi-resistant colonies of both common and tropical bed bugs (Cimex lectularius and C. hemipterus, respectively). This mutation was genetically associated with propoxur and fenitrothion resistance in F348Y-segregating colonies of C. hemipterus. Inhibition of heterologously expressed C. lectularius p-Ace with insecticides revealed that the sensitivities of F348Y-carrying AChE decreased by orders of 10- to more than 100-fold for diazoxon, carbaryl, fenitroxon, paraoxon, chlorpyrifos-methyl, malaoxon, azamethiphos, methyl-paraoxon, and propoxur. In contrast, the mutant AChE showed a slightly decreased degree of sensitivity for dichlorvos and almost unchanged sensitivity for metoxadiazone. Further studies are needed to ascertain whether the practical efficacies of dichlorvos and metoxadiazone are ensured against F348Y-carrying bed bugs and whether other resistance mechanisms are involved.
ESTHER : Komagata_2021_Insect.Biochem.Mol.Biol__103637
PubMedSearch : Komagata_2021_Insect.Biochem.Mol.Biol__103637
PubMedID: 34454015
Gene_locus related to this paper: cimle-ACHE1

Title : Effect of fish paste products, fish balls 'tsumire', intake in Sprague-Dawley rats - Kadokura_2021_J.Nutr.Sci_10_e62
Author(s) : Kadokura K , Tomita T , Suruga K
Ref : J Nutr Sci , 10 :e62 , 2021
Abstract : The fish paste product, fish balls 'tsumire', is a traditional type of Japanese food made from minced fish as well as imitation crab, kamaboko and hanpen. Although tsumire is known as a high-protein and low-fat food, there is a lack of scientific evidence on its health benefits. Hence, we aimed to investigate the effects of tsumire intake on organ weight and biomarker levels in Sprague-Dawley rats for 84 d as a preliminary study. Six-week-old male Sprague-Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5 % dried tsumire. Throughout the administration period, we monitored their body weight and food intake; at the end of this period, we measured their organ weight and analysed their blood biochemistry. No significant differences were observed with respect to body weight, food intake, organ weight and many biochemical parameters between the two groups. It was found that inorganic phosphorus and glucose levels were higher in group II rats than in group I rats. On the other hand, sodium, calcium, amylase and cholinesterase levels were significantly lower in group II than in group I. Interestingly, we found that the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase and leucine aminopeptidase in group II were significantly lower than in group I, and that other liver function parameters of group II tended to be lower than in group I. In conclusion, we consider that the Japanese traditional food, 'tsumire,' may be effective as a functional food for human health management worldwide.
ESTHER : Kadokura_2021_J.Nutr.Sci_10_e62
PubMedSearch : Kadokura_2021_J.Nutr.Sci_10_e62
PubMedID: 34457244

Title : Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms - Yumoto_2020_Mol.Autism_11_68
Author(s) : Yumoto T , Kimura M , Nagatomo R , Sato T , Utsunomiya S , Aoki N , Kitaura M , Takahashi K , Takemoto H , Watanabe H , Okano H , Yoshida F , Nao Y , Tomita T
Ref : Mol Autism , 11 :68 , 2020
Abstract : BACKGROUND: Several genetic alterations, including point mutations and copy number variations in NLGN genes, have been associated with psychiatric disorders, such as autism spectrum disorder (ASD) and X-linked mental retardation (XLMR). NLGN genes encode neuroligin (NL) proteins, which are adhesion molecules that are important for proper synaptic formation and maturation. Previously, we and others found that the expression level of murine NL1 is regulated by proteolytic processing in a synaptic activity-dependent manner. METHODS: In this study, we analyzed the effects of missense variants associated with ASD and XLMR on the metabolism and function of NL4X, a protein which is encoded by the NLGN4X gene and is expressed only in humans, using cultured cells, primary neurons from rodents, and human induced pluripotent stem cell-derived neurons. RESULTS: NL4X was found to undergo proteolytic processing in human neuronal cells. Almost all NL4X variants caused a substantial decrease in the levels of mature NL4X and its synaptogenic activity in a heterologous culture system. Intriguingly, the L593F variant of NL4X accelerated the proteolysis of mature NL4X proteins located on the cell surface. In contrast, other variants decreased the cell-surface trafficking of NL4X. Notably, protease inhibitors as well as chemical chaperones rescued the expression of mature NL4X. LIMITATIONS: Our study did not reveal whether these dysfunctional phenotypes occurred in individuals carrying NLGN4X variant. Moreover, though these pathological mechanisms could be exploited as potential drug targets for ASD, it remains unclear whether these compounds would have beneficial effects on ASD model animals and patients. CONCLUSIONS: These data suggest that reduced amounts of the functional NL4X protein on the cell surface is a common mechanism by which point mutants of the NL4X protein cause psychiatric disorders, although different molecular mechanisms are thought to be involved. Furthermore, these results highlight that the precision medicine approach based on genetic and cell biological analyses is important for the development of therapeutics for psychiatric disorders.
ESTHER : Yumoto_2020_Mol.Autism_11_68
PubMedSearch : Yumoto_2020_Mol.Autism_11_68
PubMedID: 32873342

Title : A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons - Hayashi_2016_Sci.Rep_6_23969
Author(s) : Hayashi Y , Nishimune H , Hozumi K , Saga Y , Harada A , Yuzaki M , Iwatsubo T , Kopan R , Tomita T
Ref : Sci Rep , 6 :23969 , 2016
Abstract : Notch signaling plays crucial roles for cellular differentiation during development through gamma-secretase-dependent intramembrane proteolysis followed by transcription of target genes. Although recent studies implicate that Notch regulates synaptic plasticity or cognitive performance, the molecular mechanism how Notch works in mature neurons remains uncertain. Here we demonstrate that a novel Notch signaling is involved in expression of synaptic proteins in postmitotic neurons. Levels of several synaptic vesicle proteins including synaptophysin 1 and VGLUT1 were increased when neurons were cocultured with Notch ligands-expressing NIH3T3 cells. Neuron-specific deletion of Notch genes decreased these proteins, suggesting that Notch signaling maintains the expression of synaptic vesicle proteins in a cell-autonomous manner. Unexpectedly, cGMP-dependent protein kinase (PKG) inhibitor, but not gamma-secretase inhibitor, abolished the elevation of synaptic vesicle proteins, suggesting that generation of Notch intracellular domain is dispensable for this function. These data uncover a ligand-dependent, but gamma-secretase-independent, non-canonical Notch signaling involved in presynaptic protein expression in postmitotic neurons.
ESTHER : Hayashi_2016_Sci.Rep_6_23969
PubMedSearch : Hayashi_2016_Sci.Rep_6_23969
PubMedID: 27040987

Title : Activity-dependent proteolytic cleavage of neuroligin-1 - Suzuki_2012_Neuron_76_410
Author(s) : Suzuki K , Hayashi Y , Nakahara S , Kumazaki H , Prox J , Horiuchi K , Zeng M , Tanimura S , Nishiyama Y , Osawa S , Sehara-Fujisawa A , Saftig P , Yokoshima S , Fukuyama T , Matsuki N , Koyama R , Tomita T , Iwatsubo T
Ref : Neuron , 76 :410 , 2012
Abstract : Neuroligin NLG a postsynaptic adhesion molecule is involved in the formation of synapses by binding to a cognate presynaptic ligand neurexin Here we report that neuroligin-1 NLG1 undergoes ectodomain shedding at the juxtamembrane stalk region to generate a secreted form of NLG1 and a membrane-tethered C-terminal fragment CTF in adult rat brains in vivo as well as in neuronal cultures Pharmacological and genetic studies identified ADAM10 as the major protease responsible for NLG1 shedding the latter being augmented by synaptic NMDA receptor activation or interaction with soluble neurexin ligands NLG1-CTF was subsequently cleaved by presenilin/gamma-secretase Secretion of soluble NLG1 was significantly upregulated under a prolonged epileptic seizure condition and inhibition of NLG1 shedding led to an increase in numbers of dendritic spines in neuronal cultures Collectively neuronal activity-dependent proteolytic processing of NLG1 may negatively regulate the remodeling of spines at excitatory synapses.
ESTHER : Suzuki_2012_Neuron_76_410
PubMedSearch : Suzuki_2012_Neuron_76_410
PubMedID: 23083742

Title : Overexpression of cytochrome P450 genes in pyrethroid-resistant Culex quinquefasciatus - Komagata_2010_Insect.Biochem.Mol.Biol_40_146
Author(s) : Komagata O , Kasai S , Tomita T
Ref : Insect Biochemistry & Molecular Biology , 40 :146 , 2010
Abstract : JPal-per strain of Culex quinquefasciatus exhibits extremely high resistance against pyrethroids in larvae, though the resistance is greatly lower in adults. Increased microsome monooxygenase metabolism is one of the major factors of the larval resistance in this strain. We cloned 46 novel cytochrome P450 cDNAs from JPal-per strain. An oligonucleotide microarray was designed for the novel 46 genes plus 16 previously reported P450 genes along with other non-P450 gene probes. Of these, five P450 genes were upregulated (>2.5-fold) in JPal-per larvae as compared with a susceptible strain. The expression ratios for the highest three among the five P450 genes screened in the microarray analysis, CYP9M10, CYP4H34 and CYP6Z10, were further validated by qPCR as 264-, 8.3-, and 3.9-fold, respectively. In JPal-per, the transcription levels of CYP9M10 and CYP4H34 showed a similar stage-dependent pattern as a high expression level during the larvfrom Ogasawara Islands in Japanal stage dramatically decreases in the adult stage. This larval specific overexpression manner of the two genes was consistent with the characteristic of stage-dependent resistance of JPal-per strain previously reported, suggesting that the two P450s, CYP9M10 and CYP4H34, are involved in pyrethroid detoxification in JPal-per strain.
ESTHER : Komagata_2010_Insect.Biochem.Mol.Biol_40_146
PubMedSearch : Komagata_2010_Insect.Biochem.Mol.Biol_40_146
PubMedID: 20080182
Gene_locus related to this paper: culqu-ACHE2

Title : S-palmitoylation of gamma-secretase subunits nicastrin and APH-1 - Cheng_2009_J.Biol.Chem_284_1373
Author(s) : Cheng H , Vetrivel KS , Drisdel RC , Meckler X , Gong P , Leem JY , Li T , Carter M , Chen Y , Nguyen P , Iwatsubo T , Tomita T , Wong PC , Green WN , Kounnas MZ , Thinakaran G
Ref : Journal of Biological Chemistry , 284 :1373 , 2009
Abstract : Proteolytic processing of amyloid precursor protein (APP) by beta- and gamma-secretases generates beta-amyloid (Abeta) peptides, which accumulate in the brains of individuals affected by Alzheimer disease. Detergent-resistant membrane microdomains (DRM) rich in cholesterol and sphingolipid, termed lipid rafts, have been implicated in Abeta production. Previously, we and others reported that the four integral subunits of the gamma-secretase associate with DRM. In this study we investigated the mechanisms underlying DRM association of gamma-secretase subunits. We report that in cultured cells and in brain the gamma-secretase subunits nicastrin and APH-1 undergo S-palmitoylation, the post-translational covalent attachment of the long chain fatty acid palmitate common in lipid raft-associated proteins. By mutagenesis we show that nicastrin is S-palmitoylated at Cys(689), and APH-1 is S-palmitoylated at Cys(182) and Cys(245). S-Palmitoylation-defective nicastrin and APH-1 form stable gamma-secretase complexes when expressed in knock-out fibroblasts lacking wild type subunits, suggesting that S-palmitoylation is not essential for gamma-secretase assembly. Nevertheless, fractionation studies show that S-palmitoylation contributes to DRM association of nicastrin and APH-1. Moreover, pulse-chase analyses reveal that S-palmitoylation is important for nascent polypeptide stability of both proteins. Co-expression of S-palmitoylation-deficient nicastrin and APH-1 in cultured cells neither affects Abeta40, Abeta42, and AICD production, nor intramembrane processing of Notch and N-cadherin. Our findings suggest that S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate gamma-secretase processing of APP and other substrates.
ESTHER : Cheng_2009_J.Biol.Chem_284_1373
PubMedSearch : Cheng_2009_J.Biol.Chem_284_1373
PubMedID: 19028695

Title : PCR-based identification of Culex pipiens complex collected in Japan - Kasai_2008_Jpn.J.Infect.Dis_61_184
Author(s) : Kasai S , Komagata O , Tomita T , Sawabe K , Tsuda Y , Kurahashi H , Ishikawa T , Motoki M , Takahashi T , Tanikawa T , Yoshida M , Shinjo G , Hashimoto T , Higa Y , Kobayashi M
Ref : Jpn J Infect Dis , 61 :184 , 2008
Abstract : The Culex pipiens complex consists of vector mosquitoes that transmit important human pathogens. In this study we established a simplified method to distinguish three members of the Cx. pipiens complex, Cx. p. pallens Coquillet, Cx. p. form molestus Forskal, and Cx. quinquefasciatus Say, collected in Japan. Sequence analysis of the Drosophila Ace-orthologous acetylcholinesterase (Ace) gene (668 to 680 bp) revealed that a single polymorphic region characterizes each species. Based on this region, specific primers that distinguish Cx. p. form molestus (ACEpip2) and Cx. p. pallens (ACEpall2) were newly designed. Polymerase chain reactions were performed with the genomic DNA of Culex mosquitoes as the template, and these primers clearly distinguished two Culex spp. The accuracy of the designed primers was evaluated with 38 colonies of mosquito samples collected from 9 prefectures of Japan. The testing revealed that the distribution of anautogenous Cx. p. pipiens has not been confirmed in Japan. It also revealed that the male of Cx. p. pallens possesses an Ace gene haplotype that is highly similar to the sequence of Cx. quinquefasciatus. This improved method allows the evaluation of vector competence of Cx. p.molestus, which is the suspected vector of West Nile virus.
ESTHER : Kasai_2008_Jpn.J.Infect.Dis_61_184
PubMedSearch : Kasai_2008_Jpn.J.Infect.Dis_61_184
PubMedID: 18503166

Title : Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors - Fuwa_2007_ACS.Chem.Biol_2_408
Author(s) : Fuwa H , Takahashi Y , Konno Y , Watanabe N , Miyashita H , Sasaki M , Natsugari H , Kan T , Fukuyama T , Tomita T , Iwatsubo T
Ref : ACS Chemical Biology , 2 :408 , 2007
Abstract : Divergent synthesis of multifunctional molecular probes based on caprolactam-derived dipeptidic gamma-secretase inhibitors (GSIs), Compound E (CE) and LY411575 analogue (DBZ), was efficiently accomplished by means of Cu(I)-catalyzed azide/alkyne fusion reaction. Photoaffinity labeling experiments using these derivatives coupled to photoactivatable and biotin moieties provided direct evidence that the molecular targets of CE and DBZ are the N-terminal fragment of presenilin 1 within the gamma-secretase complex. Moreover, these photoprobes directly targeted signal peptide peptidase. These data suggest that the divergent synthesis of molecular probes has been successfully applied to characterize the interaction of GSIs with their molecular targets and define the structural requirements for inhibitor binding to intramembrane-cleaving proteases.
ESTHER : Fuwa_2007_ACS.Chem.Biol_2_408
PubMedSearch : Fuwa_2007_ACS.Chem.Biol_2_408
PubMedID: 17530731

Title : Molecular characterization of two acetylcholinesterase cDNAs in Pediculus human lice - Lee_2007_J.Med.Entomol_44_72
Author(s) : Lee SW , Kasai S , Komagata O , Kobayashi M , Agui N , Kono Y , Tomita T
Ref : Journal of Medical Entomology , 44 :72 , 2007
Abstract : Two cDNA sequences encoding Drosophila Ace-orthologous and -paralogous acetylcholinesterase precursors (AO- and AP-AChE precursors, respectively), were identified from the body louse, Pediculus humanus humanus L. In vitro inhibition studies with an insecticide-susceptible body louse strain exhibited a simplex inhibitory response of AChE. The I50 values of fenitroxon and carbaryl were estimated to be 2.2 and 1.9 microM for the susceptible lice, respectively. The mRNA level of AP-AChE gene was 3.1- and 9.3-fold higher than that of AO-AChE gene in the abdomen and the combined parts of the head and thorax, respectively, suggesting, due to its abundance, the potential significance of the AP-AChE isoform in Pediculus human lice in association with the efficacy of AChE-targeting pediculicides.
ESTHER : Lee_2007_J.Med.Entomol_44_72
PubMedSearch : Lee_2007_J.Med.Entomol_44_72
PubMedID: 17294923
Gene_locus related to this paper: pedhb-ACHE1 , pedhb-ACHE2 , pedhc-ACHE1 , pedhc-ACHE2

Title : Amino acid substitutions conferring insecticide insensitivity in Ace-paralogous acetylcholinesterase - Kono_2006_Pestic.Biochem.Physiol_85_123
Author(s) : Kono Y , Tomita T
Ref : Pesticide Biochemistry and Physiology , 85 :123 , 2006
Abstract : Since insecticide insensitivity of acetylcholinesterase (AChE) was, found about 40 years ago, a cause of the resistance to organophosphates in the spider mite, more than 30 insect and Acarus species have added to the instance. Based on the 3-dimensional analysis of Torpedo AChE structure and sequencing of Drosophila AChE gene (Ace), amino acid substitutions conferring the insensitivity have been found in Drosophila melanogaster. However, no amino acid substitution responsible for the AChE insensitivity had been found in insects and Acari except Brachicera flies until the second type of AChE paralogous to Ace was discovered in Schizaphis graminus and Anopheles gambiae. Sequencing of Ace-paralogous AChE cDNAs has been followed in insect species of various orders. Now, various amino acid substitutions are found and correspond to different biochemical properties of insensitive AChEs in relation to the function of substituted amino acids in the 3-dimensional structure. Existence of two AChE genes raises questions about differentiation of the two genes, site of gene expression, and function of each enzyme.
ESTHER : Kono_2006_Pestic.Biochem.Physiol_85_123
PubMedSearch : Kono_2006_Pestic.Biochem.Physiol_85_123
PubMedID:

Title : Expression of Ace-paralogous acetylcholinesterase of Culex tritaeniorhynchus with an amino acid substitution conferring insecticide insensitivity in baculovirus-insect cell system - 0h_2006_Pestic.Biochem.Physiol_85_46
Author(s) : Oh SH , Kozaki T , Mizuno H , Tomita T , Kono Y
Ref : Pesticide Biochemistry and Physiology , 85 :46 , 2006
Abstract : In Ace paralogous acetylcholinesterase (AP-AChE) of Culex tritaeniorhynchus, an amino acid substitution, Phe455Trp, is accompanied by the insecticide insensitivity. To confirm the responsibility of the substitution to the insensitivity, AP-AChE cDNA with and without a Phe455Trp substitution and Ace orthologous AChE (AO-AChE) cDNA were expressed in a baculovirus-insect cell system and the biochemical properties of AChEs (AP-CxTI, AP-CxTS, and AO-CxT, respectively) determined. AP-CxTI which has the same level of affinity to ACh, the natural substrate, showed a drastic decline in affinity to the artificial substrates composed of a longer moiety. The sensitivity of AP-CxTI to inhibitors was extremely reduced when compared with AP-CxTS. The insensitivity to tested organophosphates was greater than to monomethyl carbamates. AO-AChE showed similar substrate specificity and a slightly higher sensitivity to inhibitors when compared with AP-CxTS. Taking the position of Phe455Trp in the acyl pocket of the active site into account, the dimensions of the acyl pocket appear to became smaller by the substitution and insensitive to inhibitors.
ESTHER : 0h_2006_Pestic.Biochem.Physiol_85_46
PubMedSearch : 0h_2006_Pestic.Biochem.Physiol_85_46
PubMedID:

Title : Two amino acid substitutions in acetylcholinesterase associated with pirimicarb and organophosphorous insecticide resistance in the cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae) - Toda_2004_Insect.Mol.Biol_13_549
Author(s) : Toda S , Komazaki S , Tomita T , Kono Y
Ref : Insect Molecular Biology , 13 :549 , 2004
Abstract : The complete coding sequences of two acetylcholinesterase (AChE) genes, Ace1 (orthologous to Drosophila Ace) and Ace2 (paralogous to Ace), from the cotton aphid (Aphis gossypii) were identified and sequences from carbamate resistant and susceptible strains compared. No change in the amino acid sequences was found in Ace1, while two amino acid substitutions, Ser431Phe and Ala302Ser, were detected between resistant and susceptible strains in Ace2. The position of Ser431Phe corresponds to one of fourteen aromatic residues lining the active site gorge and is located in the acyl pocket. Ala302Ser is located at one of the three residues which form the oxyanion hole in the active site of AChE. The Ser431Phe and Ala302Ser substitutions may play a role in pirimicarb and organophosphate resistance, respectively.
ESTHER : Toda_2004_Insect.Mol.Biol_13_549
PubMedSearch : Toda_2004_Insect.Mol.Biol_13_549
PubMedID: 15373811
Gene_locus related to this paper: aphgo-ACHE1 , aphgo-ACHE2

Title : An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus - Nabeshima_2004_Biochem.Biophys.Res.Commun_313_794
Author(s) : Nabeshima T , Mori A , Kozaki T , Iwata Y , Hidoh O , Harada S , Kasai S , Severson DW , Kono Y , Tomita T
Ref : Biochemical & Biophysical Research Communications , 313 :794 , 2004
Abstract : A cDNA sequence encoding a Drosophila Ace-paralogous acetylcholinesterase (AChE) precursor of 701 amino acid residues was identified as the second AChE gene (Ace2) transcript from Culex tritaeniorhynchus. The Ace2 gene is tightly linked to organophosphorus insecticide (OP)-insensitivity of AChE on chromosome 2. The cDNA sequences were compared between an insecticide-susceptible strain and the resistant strain, TYM, that exhibits a 870-fold decrease in fenitroxon-sensitivity of AChE. Two amino acid substitutions were present in TYM mosquitoes. One is F455W whose homologous position in Torped AChE (Phe331) is located in the vicinity of the catalytic His in the acyl pocket of the active site gorge. The other substitution is located to a C-terminal Ile697 position that apparently seems to be excluded from the mature protein and is irrelevant to catalytic activity. The F455W replacement in the Ace2 gene is solely responsible for the insecticide-insensitivity of AChE in TYM mosquitoes.
ESTHER : Nabeshima_2004_Biochem.Biophys.Res.Commun_313_794
PubMedSearch : Nabeshima_2004_Biochem.Biophys.Res.Commun_313_794
PubMedID: 14697262
Gene_locus related to this paper: cultr-ACHE1 , cultr-ACHE2

Title : An amino acid substitution on the second acetylcholinesterase in the pirimicarb-resistant strains of the peach potato aphid, Myzus persicae - Nabeshima_2003_Biochem.Biophys.Res.Commun_307_15
Author(s) : Nabeshima T , Kozaki T , Tomita T , Kono Y
Ref : Biochemical & Biophysical Research Communications , 307 :15 , 2003
Abstract : cDNAs encoding two acetylcholinesterases (AChEs) were isolated from the peach potato aphid, Myzus persicae. MpAChE1 was orthologous and MpAChE2 was paralogous with the ace of Drosophila melanogaster. The deduced amino acid sequence of MpAChE1 cDNA was identical between the pirimicarb susceptible and resistant strains. However, a single amino acid substitution of Ser431Phe on MpAchE2 was found in the pirimicarb resistant strains. This substitution was located in the acyl pocket of the enzyme and was thought to alter the ligand specificity.
ESTHER : Nabeshima_2003_Biochem.Biophys.Res.Commun_307_15
PubMedSearch : Nabeshima_2003_Biochem.Biophys.Res.Commun_307_15
PubMedID: 12849975
Gene_locus related to this paper: myzpe-ACHE , myzpe-ACHEm

Title : cDNA and deduced proteine sequence of acetylcholinesterase from the diamond back moth Plutella xylostella (L.) (Lepidoptera: Plutellidae) -
Author(s) : Ni XY , Tomita T , Kasai S , Kono Y
Ref : Appl Entomol Zool , 38 :49 , 2003
PubMedID:
Gene_locus related to this paper: pluxy-ACHE

Title : Sequence of a cDNA encoding acetylcholinesterase from susceptible and resistant two-spotted spider mite, Tetranychus urticae - Anazawa_2003_Insect.Biochem.Mol.Biol_33_509
Author(s) : Anazawa Y , Tomita T , Aiki Y , Kozaki T , Kono Y
Ref : Insect Biochemistry & Molecular Biology , 33 :509 , 2003
Abstract : Acetylcholinesterase (AChE) from two-spotted spider mites, Tetranychus urticae was compared between an organophosphate susceptible (TKD) and a resistant (NCN) strain. The AChE of TKD had lower affinity to acetylthiocholine and propionylthiocholine than that of NCN, and the inhibition of AChE by DDVP, ambenonium, eserine and n-methyl-eserine showed that NCN was more insensitive than TKD. AChE cDNA sequence was determined, and the 687 amino acids of primary structure were deduced. There were six replacements of amino acid residues in TKD and two in NCN. #F331(439)C was the only substitution unique to NCN, however, this mutation existed homozygously in only two out of nine mites. This residue is one of the gorge lining components, and #F331(439)C might act an important role in the sensitivity of AChE to the inhibitors.
ESTHER : Anazawa_2003_Insect.Biochem.Mol.Biol_33_509
PubMedSearch : Anazawa_2003_Insect.Biochem.Mol.Biol_33_509
PubMedID: 12706630
Gene_locus related to this paper: tetur-ACHE

Title : Linkage analysis of an acetylcholinesterase gene in the house fly Musca domestica (Diptera: Muscidae) - Kozaki_2002_J.Econ.Entomol_95_129
Author(s) : Kozaki O , Shono T , Tomita T , Taylor D , Kono Y
Ref : J Econ Entomol , 95 :129 , 2002
Abstract : Linkage of an acetylcholinesterase (AChE) gene was detected in the house fly, Musca domestica L., by using the backcross method between a strain, aabys, that had a morphological multichromosomal marker on each of the five autosomes and a wild strain, LPR. Both strains were homozygous in this gene, and we used eight single nucleotide polymorphisms (SNPs) between them to distinguish the parental sequences in the backcrossed progeny, two of which resulted in the amino acid substitiutions common to the Drosophila and Aedes AChEs insensitive to organophosphates and carbamates. F, appeared to be a wild phenotype, and the AChE gene was heterozyous of aabys and LPR. In the backcross progeny, 32 (2(5)) phenotypes appeared, and 10 phenotypes with one wild or morphological marker were picked up for genotyping by the SNPs of AChE gene. A combination of the morphological markers and the SNPs revealed that the AChE structural gene is linked to autosome 2 in the house fly.
ESTHER : Kozaki_2002_J.Econ.Entomol_95_129
PubMedSearch : Kozaki_2002_J.Econ.Entomol_95_129
PubMedID: 11942747
Gene_locus related to this paper: musdo-ACHE

Title : A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface - Leem_2002_Neurobiol.Dis_11_64
Author(s) : Leem JY , Saura CA , Pietrzik C , Christianson J , Wanamaker C , King LT , Veselits ML , Tomita T , Gasparini L , Iwatsubo T , Xu H , Green WN , Koo EH , Thinakaran G
Ref : Neurobiol Dis , 11 :64 , 2002
Abstract : Presenilin 1 (PS1) and presenilin 2 play a critical role in the gamma-secretase processing of amyloid precursor protein (APP) and Notch1. Here, we investigate maturation and intracellular trafficking of APP and other membrane proteins in cells expressing an experimental PS1 deletion mutant (deltaM1,2). Stable expression of deltaM1,2 impairs gamma-secretase processing of Notch1 and delays Abeta secretion. Kinetic studies show enhanced O-glycosylation and sialylation of holo-APP and marked accumulation of APP COOH-terminal fragments (CTFs). Surface biotinylation, live staining, and trafficking studies show increased surface accumulation of holo-APP and CTFs in deltaM1,2 cells resulting from enhanced surface delivery of newly synthesized APP. Expression of a loss-of-function PS1 mutant (D385A) or incubation of cells with gamma-secretase inhibitors also increases surface levels of holo-APP and CTFs. In contrast to APP, glycosylation and surface accumulation of another type I membrane protein, nicastrin, are markedly reduced in deltaM1,2 cells. Finally, expression of deltaM1,2 results in the increased assembly and surface expression of nicotinic acetylcholine receptors, illustrating that PS1's influence on protein trafficking extends beyond APP and other type I membrane protein substrates of gamma-secretase. Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins.
ESTHER : Leem_2002_Neurobiol.Dis_11_64
PubMedSearch : Leem_2002_Neurobiol.Dis_11_64
PubMedID: 12460547

Title : Comparative linkage map development and identification of an autosomal locus for insensitive acetylcholinesterase-mediated insecticide resistance in Culex tritaeniorhynchus - Mori_2001_Insect.Mol.Biol_10_197
Author(s) : Mori A , Tomita T , Hidoh O , Kono Y , Severson DW
Ref : Insect Molecular Biology , 10 :197 , 2001
Abstract : A comparative linkage map for Culex tritaeniorhynchus was constructed based on restriction fragment length polymorphism markers using cDNAs from Aedes aegypti. Linear orders of marker loci in Cx. tritaeniorhynchus were identical to Culex pipiens wherein chromosomes 2 and 3 reflect whole-arm rearrangements compared to A. aegypti. However, the sex determination locus in Cx. tritaeniorhynchus maps to chromosome 3, in contrast to Cx. pipiens and Ae. aegypti where it is located on chromosome 1. Our results indicate that insensitive acetylcholinesterase (AChE)-mediated organophosphate resistance is controlled by a single major gene (AChE) on chromosome 2, while the AChE structural gene (Ace) is located on chromosome 1. No evidence for a second Ace gene was observed, even under very low stringency hybridization conditions.
ESTHER : Mori_2001_Insect.Mol.Biol_10_197
PubMedSearch : Mori_2001_Insect.Mol.Biol_10_197
PubMedID: 11437911

Title : Fenitroxon insensitive acetylcholinesterases of the housefly, Musca domestica associated with point mutations - Kozaki_2001_Insect.Biochem.Mol.Biol_31_991
Author(s) : Kozaki T , Shono T , Tomita T , Kono Y
Ref : Insect Biochemistry & Molecular Biology , 31 :991 , 2001
Abstract : The cDNA of AChE in the housefly, Musca domestica, was sequenced and individual flies were genotyped by this gene in an inhibition assay of AChE activity with an organophaspate, fenitroxon. Mutations at Gly(342) and Tyr(407), which are reportedly conserved in resistant strains of Drosophila, were associated with the insensitivity to fenitroxon. Two other mutations, Ile(162) and Val(260), did not have an apparent effect on insensitivity. However, the four mutations are located in the active site of the enzyme, and therefore the non-neutral mutations in this gene are considered to cause the insensitivity of AChE in the development of insecticide resistance of the housefly.
ESTHER : Kozaki_2001_Insect.Biochem.Mol.Biol_31_991
PubMedSearch : Kozaki_2001_Insect.Biochem.Mol.Biol_31_991
PubMedID: 11483435
Gene_locus related to this paper: musdo-ACHE

Title : Absence of protein polymorphism attributable to insecticide-insensitivity of acetylcholinesterase in the green rice leafhopper, Nephotettix cincticeps - Tomita_2000_Insect.Biochem.Mol.Biol_30_325
Author(s) : Tomita T , Hidoh O , Kono Y
Ref : Insect Biochemistry & Molecular Biology , 30 :325 , 2000
Abstract : The cDNA sequence of acetylcholinesterase (AChE) from the green rice leafhopper, Nephotettix cincticeps, was amplified, based on conserved peptide sequences of AChEs. A 2.3 kb contiguous sequence, containing an ORF encoding an AChE precursor with 677 amino acid residues was obtained. The deduced protein sequence showed the most similarity to that of AChE in the Colorado potato beetle, having common features in the primary AChE structure. cDNA sequences of individual leafhoppers from an insecticide susceptible strain and the resistant strain Nakagawara, whose methylcarbamate-insensitive AChEs show 10(2) or more I(50) ratio for propoxur, were compared. No fixed inter-strain difference was identified in the protein sequence, though amino acid substitution polymorphism was found at one position in the susceptible strain. Insecticide-insensitivity of leafhopper AChE does not result from changes in the protein primary structure that is encoded by the AChE gene sequence isolated in this study.
ESTHER : Tomita_2000_Insect.Biochem.Mol.Biol_30_325
PubMedSearch : Tomita_2000_Insect.Biochem.Mol.Biol_30_325
PubMedID: 10727899
Gene_locus related to this paper: nepci-ACHE

Title : Molecular properties and activity of a carboxyl-terminal truncated form of xylanase 3 from Aeromonas caviae W-61 - Okai_1998_Biosci.Biotechnol.Biochem_62_1560
Author(s) : Okai N , Fukasaku M , Kaneko J , Tomita T , Muramoto K , Kamio Y
Ref : Biosci Biotechnol Biochem , 62 :1560 , 1998
Abstract : Aeromonas caviae W-61 produces five species of xylanases, xylanases 1, 2, 3, 4, and 5 [Nguyen, V.D. et al., Biosci. Biotechnol. Biochem., 56, 1708-1712 (1993) and Appl. Environ. Microbiol., 57, 445-449 (1991)]. While preserving a purified xylanase 3 preparation from A. caviae in solution at 4 degrees C, the xylanase 3 was found to be proteolyzed to give a truncated form with a smaller molecular mass than that of the intact one. It appears likely that the truncated form of xylanase 3 was produced in this particular purification experiment by the action of a contaminating protease. We isolated the truncated form of xylanase 3 (Xyn3tr), of which the C-terminal 102-residue segment is missing. By the chemical analysis of the N- and C-terminal amino acid residues of Xyn3tr and the DNA sequencing analysis of the xylanase 3 gene (xyn3), the N-terminal 398th proline residue of xylanase 3 was found to be the C-terminus of Xyn3tr. Xyn3tr had the activity to form xylotriose (X3), xylotetraose (X4), xylopentaose (X5), and xylohexaose (X6) as main final products from oat spelt xylan. In contrast, intact xylanase 3 released X6 and higher xylo-oligosaccharides as main products. Xylanase 3 hydrolysed X4 through X6. However, Xyn3tr had no activity towards X4 and X5. The recombinant Xyn3tr and recombinant xylanase 3 (XYN3) were purified homogeneously from the periplasmic space of E. coli harboring the plasmids pXYN3 and pXYN3tr, which include xyn3 and xyn3tr genes, respectively, and their enzymatic activities were measured. The cleavage patterns of oat spelt and xylo-oligosaccharides by XYN3tr were identical with that by intact Xyn3tr. Thus, we conclude that the C-terminal region comprising a 102-residue segment in xylanase 3 is involved in governing the molecular size of xylo-oligosaccharides cleaved from beta-1,4-xylan by the enzyme and in the hydrolytic activity towards X4 and X5.
ESTHER : Okai_1998_Biosci.Biotechnol.Biochem_62_1560
PubMedSearch : Okai_1998_Biosci.Biotechnol.Biochem_62_1560
PubMedID: 9757562

Title : Cholesterol-mediated changes of neutral cholesterol esterase activity in macrophages. Mechanism for mobilization of cholesteryl esters in lipid droplets by HDL - Miura_1997_Arterioscler.Thromb.Vasc.Biol_17_3033
Author(s) : Miura S , Chiba T , Mochizuki N , Nagura H , Nemoto K , Tomita I , Ikeda M , Tomita T
Ref : Arterioscler Thromb Vasc Biol , 17 :3033 , 1997
Abstract : Cholesteryl esters (CE) in lipid droplets undergo a continual cycle of hydrolysis and reesterification by neutral cholesterol esterase (N-CEase) and acyl CoA:cholesterol acyltransferase (ACAT), respectively. The mechanism by which HDL mobilizes CE from lipid droplets in J774 A.1 cells was investigated, focusing on N-CEase activity. We asked whether HDL enhances the activity and, if so, what signals induce the change of the activity. An incubation of cells with HDL enhanced the decline of cholesteryl-[l-14C]-oleate in foam cells and increased N-CEase activity in the supernatant of cell homogenate in a concentration-dependent manner, whereas incubation with LDL decreased the activity. In addition, N-CEase activity was fivefold higher when cells were cultured in 10% lipoprotein-deficient serum (LPDS) medium (2 micrograms cholesterol/mL) than when cultured in 10% fetal calf serum medium (31 micrograms cholesterol/mL), suggesting that changes in N-CEase activity are mediated by cholesterol. An addition of cholesterol (0 to 30 micrograms/mL) in LPDS medium markedly inhibited N-CEase activity with a concomitant increase in cellular cholesterol concentration. This inhibitory effect of cholesterol was also observed in mouse peritoneal macrophages. In vitro addition of cholesterol did not affect N-CEase activity. Treatment of cells with HMG-CoA reductase inhibitors enhanced N-CEase activity, whereas ACAT inhibitor decreased the activity. Northern blot analysis of N-CEase mRNA showed that the expression was not altered by the presence of cholesterol in LPDS medium. These results suggest that cholesterol downregulates N-CEase activity, probably through cholesterol-dependent appearance of some factors.
ESTHER : Miura_1997_Arterioscler.Thromb.Vasc.Biol_17_3033
PubMedSearch : Miura_1997_Arterioscler.Thromb.Vasc.Biol_17_3033
PubMedID: 9409290

Title : Molecular mechanisms involved in increased expression of a cytochrome P450 responsible for pyrethroid resistance in the housefly, Musca domestica - Tomita_1995_Insect.Mol.Biol_4_135
Author(s) : Tomita T , Liu N , Smith FF , Sridhar P , Scott JG
Ref : Insect Molecular Biology , 4 :135 , 1995
Abstract : Cytochrome P450 Ipr is a developmentally regulated P450 responsible for monooxygenase-mediated pyrethroid resistance in the LPR strain of housefly. CYP6D1, the gene coding for P450 Ipr, has recently been sequenced. We investigated the molecular basis for CYP6D1-mediated pyrethroid resistance by comparison of mRNA levels, gene sequences, and gene copy number between LPR and pyrethroid susceptible strains of housefly. CYP6D1 mRNA levels were elevated in the LPR strain to a similar level as P450 Ipr protein, suggesting that over-expression of this important P450 in the resistant strain is probably due to increased transcription. Southern blots of susceptible and LPR strain DNA suggest that gene amplification is probably not involved in the increased expression of CYP6D1 protein. Five alleles of CYP6D1 were discovered and their possible role in resistance is discussed.
ESTHER : Tomita_1995_Insect.Mol.Biol_4_135
PubMedSearch : Tomita_1995_Insect.Mol.Biol_4_135
PubMedID: 8589839

Title : The regulation of cholesteryl ester metabolism by 17 beta-estradiol in macrophages. Activation of neutral cholesterol esterase - Tomita_1995_Ann.N.Y.Acad.Sci_748_637
Author(s) : Tomita T , Sawamura F , Uetsuka R , Ikeda M , Tomita I
Ref : Annals of the New York Academy of Sciences , 748 :637 , 1995
Abstract : The mechanism for antiatherogenic effects of 17 beta-estradiol (E2) was investigated in J774 A.1 cells incubated with beta-VLDL. E2 at physiological concentrations (0.25 and 2.5 nM) inhibited an accumulation of cellular cholesteryl esters and enhanced their hydrolysis in foam cells. These phenomena were preceded by activation of neutral cholesterol esterase through an increase in cyclic AMP-dependent protein kinase activity. 17 alpha-estradiol, progesterone, and testosterone lacked such stimulatory effects on neutral cholesteryl esterase.
ESTHER : Tomita_1995_Ann.N.Y.Acad.Sci_748_637
PubMedSearch : Tomita_1995_Ann.N.Y.Acad.Sci_748_637
PubMedID: 7695221