Watanabe M

References (45)

Title : Impact of Total Parenteral Nutrition on Preoperative Management of Pediatric Living-Donor Liver Transplantation for Biliary Atresia Under 2 Years Old - Ueno_2024_Transplant.Proc__
Author(s) : Ueno T , Takase K , Deguchi K , Nomura M , Watanabe M , Kamiyama M , Tazuke Y , Kimura T , Okuyama H
Ref : Transplant Proc , : , 2024
Abstract : BACKGROUND: Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. METHODS: Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. RESULTS: Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P = .0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. CONCLUSIONS: Pre-transplant TPN was safe and effective for patients with end-stage BA.
ESTHER : Ueno_2024_Transplant.Proc__
PubMedSearch : Ueno_2024_Transplant.Proc__
PubMedID: 38326201

Title : Glyoxal fixation: An approach to solve immunohistochemical problem in neuroscience research - Konno_2023_Sci.Adv_9_eadf7084
Author(s) : Konno K , Yamasaki M , Miyazaki T , Watanabe M
Ref : Sci Adv , 9 :eadf7084 , 2023
Abstract : The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized neuronal components, such as ionotropic receptors at the postsynapse and voltage-gated ion channels at the axon initial segment, often requiring additional antigen-exposing techniques to detect their authentic signals. To solve this problem, we used glyoxal, a two-carbon atom di-aldehyde. We found that glyoxal fixation greatly improved antibody penetration and immunoreactivity, uncovering signals for buried molecules by conventional immunohistochemical procedures at light and electron microscopic levels. It also enhanced immunosignals of most other molecules, which are known to be detectable in formaldehyde-fixed sections. Furthermore, we unearthed several specific primary antibodies that were once judged to be unusable in formaldehyde-fixed tissues, allowing us to successfully localize so far controversial synaptic adhesion molecule Neuroligin 1. Thus, glyoxal is a highly effective fixative for immunostaining, and a side-by-side comparison of glyoxal and formaldehyde fixation is recommended for routine immunostaining in neuroscience research.
ESTHER : Konno_2023_Sci.Adv_9_eadf7084
PubMedSearch : Konno_2023_Sci.Adv_9_eadf7084
PubMedID: 37450597

Title : Metabolic profiling, antioxidant, and enzyme inhibition potential of Iris pseudacorus L. from Egypt and Japan: A comparative study - Yehia_2023_Sci.Rep_13_5233
Author(s) : Yehia SM , Ayoub IM , Watanabe M , Devkota HP , Singab ANB
Ref : Sci Rep , 13 :5233 , 2023
Abstract : Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against alpha-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human alpha-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC(50) values of 40.89 microg/mL and 97.97 microg/mL, respectively (Trolox IC(50) value was 14.59 microg/mL). Moreover, IPR-J and IPR-E exhibited promising alpha-glucosidase inhibitory activity displaying IC(50) values of 18.52 microg/mL, 57.89 microg/mL, respectively being more potent as compared to acarbose with IC(50) value of 362.088 microg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC(50) values of 2.35, 4.81, 2.22 and 0.42 microg/mL, respectively compared to cetilistat with IC(50) value of 7.47 microg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 microg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human alpha-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.
ESTHER : Yehia_2023_Sci.Rep_13_5233
PubMedSearch : Yehia_2023_Sci.Rep_13_5233
PubMedID: 36997571

Title : In situ localization of diacylglycerol lipase alpha and beta producing an endocannabinoid 2-arachidonoylglycerol and of cannabinoid receptor 1 in the primary oocytes of postnatal mice - Kamnate_2021_J.Anat__
Author(s) : Kamnate A , Sirisin J , Polsan Y , Chomphoo S , Watanabe M , Kondo H , Hipkaeo W
Ref : Journal of Anatomy , : , 2021
Abstract : In order to understand the mechanism of the endocannabinoid (eCB) signal, which has so far been shown to work in oocyte genesis and maturation, it is critical to clarify detailed localization of the eCB synthesizing enzyme molecules as well as receptors for eCBs in oocytes in the ovary in situ. For this purpose, diacylglycerol lipase (DGL) alpha and beta are involved in the synthesis of an eCB 2-arachidonoylglycerol (2-AG). DGLalpha/beta and the cannabinoid receptor 1 (CB1) for 2-AG were shown to be localized to the primary oocytes of postnatal mice using immuno-light and electron microscopy. It was found that two types of localization existed: first, immunoreactivities for DGLalpha and beta were weakly detected throughout the ooplasm in light microscopy for which the intracellular membranes of vesicles forming tiny scattered aggregates were responsible. Secondly, DGLbeta-immunoreactivity was distinctly confined to the nuage of Balbiani bodies and small nuage-derivative structures; both amorphous materials and membranes of vesicles were responsible for their localization. On the other hand, the weak immunoreactivity for CB1 was localized in a pattern similar to the first one for DGLs, but not found in a pattern for the Balbiani nuage. Two routes of functional exertion of 2-AG synthesized by DGLs were suggested from the two types of localization: one was that the eCB synthesized at all the sites of DGLs is released from the oocytes and exerts paracrine or autocrine effects on adjacent intra-ovarian cells as well as the oocytes themselves. The other was that the eCB synthesized within the nuage was involved in the modulation of the posttranscriptional processing of oocytes. Owing to the failure in the detection of CB1 in the Balbiani nuage, however, the validity of the latter possibility remains to be elucidated.
ESTHER : Kamnate_2021_J.Anat__
PubMedSearch : Kamnate_2021_J.Anat__
PubMedID: 33398893
Gene_locus related to this paper: human-DAGLA , human-DAGLB , mouse-DGLB , mouse-q6wqj1

Title : An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum - Lai_2021_Front.Neural.Circuits_15_676891
Author(s) : Lai ESK , Nakayama H , Miyazaki T , Nakazawa T , Tabuchi K , Hashimoto K , Watanabe M , Kano M
Ref : Front Neural Circuits , 15 :676891 , 2021
Abstract : Neuroligin is a postsynaptic cell-adhesion molecule that is involved in synapse formation and maturation by interacting with presynaptic neurexin. Mutations in neuroligin genes, including the arginine to cystein substitution at the 451st amino acid residue (R451C) of neuroligin-3 (NLGN3), have been identified in patients with autism spectrum disorder (ASD). Functional magnetic resonance imaging and examination of post-mortem brain in ASD patients implicate alteration of cerebellar morphology and Purkinje cell (PC) loss. In the present study, we examined possible association between the R451C mutation in NLGN3 and synaptic development and function in the mouse cerebellum. In NLGN3-R451C mutant mice, the expression of NLGN3 protein in the cerebellum was reduced to about 10% of the level of wild-type mice. Elimination of redundant climbing fiber (CF) to PC synapses was impaired from postnatal day 10-15 (P10-15) in NLGN3-R451C mutant mice, but majority of PCs became mono-innervated as in wild-type mice after P16. In NLGN3-R451C mutant mice, selective strengthening of a single CF relative to the other CFs in each PC was impaired from P16, which persisted into juvenile stage. Furthermore, the inhibition to excitation (I/E) balance of synaptic inputs to PCs was elevated, and calcium transients in the soma induced by strong and weak CF inputs were reduced in NLGN3-R451C mutant mice. These results suggest that a single point mutation in NLGN3 significantly influences the synapse development and refinement in cerebellar circuitry, which might be related to the pathogenesis of ASD.
ESTHER : Lai_2021_Front.Neural.Circuits_15_676891
PubMedSearch : Lai_2021_Front.Neural.Circuits_15_676891
PubMedID: 34262438
Gene_locus related to this paper: human-NLGN3

Title : Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus - Uchigashima_2020_J.Biol.Chem__
Author(s) : Uchigashima M , Leung M , Watanabe T , Cheung A , Le T , Pallat S , Dinis ALM , Watanabe M , Imamura Kawasawa Y , Futai K
Ref : Journal of Biological Chemistry , : , 2020
Abstract : Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, transsynaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate Neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.
ESTHER : Uchigashima_2020_J.Biol.Chem__
PubMedSearch : Uchigashima_2020_J.Biol.Chem__
PubMedID: 32381505

Title : Safety and pharmacokinetic profiles of MGS0274 besylate (TS-134), a novel metabotropic glutamate 2\/3 receptor agonist prodrug, in healthy subjects - Watanabe_2020_Br.J.Clin.Pharmacol_86_2286
Author(s) : Watanabe M , Marcy B , Kinoshita K , Fukasawa M , Hikichi H , Chaki S , Okuyama S , Gevorkyan H , Yoshida S
Ref : British Journal of Clinical Pharmacology , 86 :2286 , 2020
Abstract : AIMS: The safety and pharmacokinetics of single and multiple doses of a novel mGlu(2/3) receptor agonist prodrug, MGS0274 besylate (TS-134), were investigated in healthy subjects. METHODS: Phase 1 single-ascending dose (5-20 mg) and multiple-ascending dose titration (5-80 mg) studies were conducted in healthy male and female subjects. Both studies were randomized, double-blinded and placebo-controlled. In one cohort of single-ascending dose study (10 mg), concentrations of MGS0008, the active compound, in the cerebrospinal fluid (CSF) were measured for up to 24 hours postdose. RESULTS: Following single and multiple oral administrations, MGS0274 was rapidly absorbed and extensively converted into MGS0008, which reached a maximum concentration (C(max) ) in plasma within 4 hours postdose and declined with a terminal half-life (t(1/2) ) of around 10 hours. Plasma exposure to MGS0274 was minimal, accounting for approximately 3% of the area under the concentration-time curve (AUC) of MGS0008. Plasma C(max) and AUC of MGS0008 at steady state increased dose proportionally (5-80 mg). MGS0008 penetrated into CSF, with a CSF-to-plasma C(max) ratio of 3.66%, and was eliminated with a t(1/2) of approximately 16 hours. The most frequent treatment-emergent adverse events observed following single and multiple oral administration included headache, nausea, somnolence, dizziness and vomiting. CONCLUSION: TS-134 is orally bioavailable in humans and converts rapidly and extensively to MGS0008, which exhibits good CSF penetration. Orally administered TS-134 was safe and generally well-tolerated; hence, TS-134 is a promising candidate for further clinical development for the treatment of disorders in which glutamatergic abnormalities are involved, such as schizophrenia.
ESTHER : Watanabe_2020_Br.J.Clin.Pharmacol_86_2286
PubMedSearch : Watanabe_2020_Br.J.Clin.Pharmacol_86_2286
PubMedID: 32353162

Title : Specific Neuroligin3-alphaNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus - Uchigashima_2020_Elife_9_
Author(s) : Uchigashima M , Konno K , Demchak E , Cheung A , Watanabe T , Keener DG , Abe M , Le T , Sakimura K , Sasaoka T , Uemura T , Imamura Kawasawa Y , Watanabe M , Futai K
Ref : Elife , 9 : , 2020
Abstract : Synapse formation and regulation require signaling interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the alphaNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic alphaNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn signaling generates distinct functional properties at synapses.
ESTHER : Uchigashima_2020_Elife_9_
PubMedSearch : Uchigashima_2020_Elife_9_
PubMedID: 33355091

Title : Labilibaculum antarcticum sp. nov., a novel facultative anaerobic, psychrotorelant bacterium isolated from marine sediment of Antarctica - Watanabe_2020_Antonie.Van.Leeuwenhoek_113_349
Author(s) : Watanabe M , Kojima H , Fukui M
Ref : Antonie Van Leeuwenhoek , 113 :349 , 2020
Abstract : A novel facultative anaerobic and facultative psychrophilic bacterium, designated SPP2(T), was isolated from an Antarctic marine sediment. Cells of the isolate were observed to be long rods (0.5 x 5-10 mum), Gram-stain negative and to have gliding motility. For growth, the optimum NaCl concentration was found to be 2-3% and the optimum temperature to be 18-22 degrees C. Strain SPP2(T) cannot use sulfate and nitrate as electron acceptors in the presence of lactate. The G+C content of the genomic DNA was determined to be 36.0 mol%.. The major cellular fatty acids were identified as anteiso-C15:0 and iso-C15:0. MK-7 was found to be the predominant respiratory quinone. Phylogenetic analysis based on the 16S rRNA gene revealed that the novel strain belongs to the family Marinifilaceae and to be closely related to Labilibaculum manganireducens 59.10-2M(T) with 16S rRNA gene sequence identity of 98%. The OrthoANI and dDDH values between the genome sequences of strain SPP2(T) and its close relative were 84% and 27.3%, which are lower than the threshold values for species delineation. On the basis of phylogenetic and phenotypic characterisation, Labilibaculum antarcticum sp. nov. is proposed with the type strain SPP2(T) (= NBRC 111151(T) = CECT 9460(T)).
ESTHER : Watanabe_2020_Antonie.Van.Leeuwenhoek_113_349
PubMedSearch : Watanabe_2020_Antonie.Van.Leeuwenhoek_113_349
PubMedID: 31628625
Gene_locus related to this paper: 9bact-a0a1y1ckm2

Title : Structural insights into modulation and selectivity of transsynaptic neurexin-LRRTM interaction - Yamagata_2018_Nat.Commun_9_3964
Author(s) : Yamagata A , Goto-Ito S , Sato Y , Shiroshima T , Maeda A , Watanabe M , Saitoh T , Maenaka K , Terada T , Yoshida T , Uemura T , Fukai S
Ref : Nat Commun , 9 :3964 , 2018
Abstract : Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1beta-LRRTM2 complex at 3.4 A resolution. The Nrxn1beta-LRRTM2 interface involves Ca(2+)-mediated interactions and overlaps with the Nrxn-neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.
ESTHER : Yamagata_2018_Nat.Commun_9_3964
PubMedSearch : Yamagata_2018_Nat.Commun_9_3964
PubMedID: 30262834

Title : Complete genome sequence of Marinifilaceae bacterium strain SPP2, isolated from the Antarctic marine sediment - Watanabe_2017_Mar.Genomics_39_1
Author(s) : Watanabe M , Kojima H , Fukui M
Ref : Marine Genomics , 39 :1 , 2018
Abstract : Abstract: Marinifilaceae bacterium strain SPP2 is a Gram-negative facultative anaerobe, isolated from the Antarctic marine sediment. Here, we present the complete genome sequence of Marinifilaceae bacterium strain SPP2, which consists of 5,718,991bp with a G+C content of 35.99%. The genome data provides insights of microbial evolution and adaption in the Antarctic marine ecosystem.
ESTHER : Watanabe_2017_Mar.Genomics_39_1
PubMedSearch : Watanabe_2017_Mar.Genomics_39_1
PubMedID:
Gene_locus related to this paper: 9bact-a0a1y1cg46 , 9bact-a0a1y1cg94

Title : Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease - Mizuma_2017_Autoimmunity_50_386
Author(s) : Mizuma T , Watanabe M , Inoue N , Arakawa Y , Tomari S , Hidaka Y , Iwatani Y
Ref : Autoimmunity , 50 :386 , 2017
Abstract : Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137 HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p = .0277), and the proportion of CD4+ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p = .0107). The TG rs2703013 TT genotype was less frequent in AITD (p = .0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p = .0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p = .0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p = .0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p = .0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb.
ESTHER : Mizuma_2017_Autoimmunity_50_386
PubMedSearch : Mizuma_2017_Autoimmunity_50_386
PubMedID: 28675712

Title : Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures - Uchigashima_2016_Proc.Natl.Acad.Sci.U.S.A_113_4206
Author(s) : Uchigashima M , Ohtsuka T , Kobayashi K , Watanabe M
Ref : Proc Natl Acad Sci U S A , 113 :4206 , 2016
Abstract : Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor alpha1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets.
ESTHER : Uchigashima_2016_Proc.Natl.Acad.Sci.U.S.A_113_4206
PubMedSearch : Uchigashima_2016_Proc.Natl.Acad.Sci.U.S.A_113_4206
PubMedID: 27035941

Title : Genome evolution in the allotetraploid frog Xenopus laevis - Session_2016_Nature_538_336
Author(s) : Session AM , Uno Y , Kwon T , Chapman JA , Toyoda A , Takahashi S , Fukui A , Hikosaka A , Suzuki A , Kondo M , van Heeringen SJ , Quigley I , Heinz S , Ogino H , Ochi H , Hellsten U , Lyons JB , Simakov O , Putnam N , Stites J , Kuroki Y , Tanaka T , Michiue T , Watanabe M , Bogdanovic O , Lister R , Georgiou G , Paranjpe SS , van Kruijsbergen I , Shu S , Carlson J , Kinoshita T , Ohta Y , Mawaribuchi S , Jenkins J , Grimwood J , Schmutz J , Mitros T , Mozaffari SV , Suzuki Y , Haramoto Y , Yamamoto TS , Takagi C , Heald R , Miller K , Haudenschild C , Kitzman J , Nakayama T , Izutsu Y , Robert J , Fortriede J , Burns K , Lotay V , Karimi K , Yasuoka Y , Dichmann DS , Flajnik MF , Houston DW , Shendure J , DuPasquier L , Vize PD , Zorn AM , Ito M , Marcotte EM , Wallingford JB , Ito Y , Asashima M , Ueno N , Matsuda Y , Veenstra GJ , Fujiyama A , Harland RM , Taira M , Rokhsar DS
Ref : Nature , 538 :336 , 2016
Abstract : To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.
ESTHER : Session_2016_Nature_538_336
PubMedSearch : Session_2016_Nature_538_336
PubMedID: 27762356
Gene_locus related to this paper: xenla-a0a1l8f4t7 , xenla-a0a1l8fbc6 , xenla-a0a1l8fct2 , xenla-q2tap9 , xenla-q4klb6 , xenla-q5xh09 , xenla-q6ax59 , xenla-q6dcw6 , xenla-q6irp4 , xenla-q6pad5 , xenla-q7sz70 , xenla-Q7ZXQ6 , xenla-q66kx1 , xenla-q640y7 , xenla-q642r3 , xenla-Q860X9 , xenla-BCHE2 , xenla-a0a1l8g7v4 , xenla-a0a1l8g1u7 , xenla-a0a1l8fmc5 , xenla-a0a1l8g467 , xenla-a0a1l8g4e4 , xenla-a0a1l8ga66 , xenla-a0a1l8gaw4 , xenla-a0a1l8gt68 , xenla-a0a1l8h0b2 , xenla-a0a1l8fdr1 , xenla-a0a1l8fdt7 , xenla-a0a1l8fi72 , xenla-a0a1l8fi73 , xenla-a0a1l8fi77 , xenla-a0a1l8fi96 , xenla-a0a1l8hc38 , xenla-a0a1l8hn27 , xenla-a0a1l8hry6 , xenla-a0a1l8hw96 , xenla-a0a1l8i2x6 , xenla-a0a1l8hei7 , xenla-a0a1l8gnd1 , xenla-a0a1l8i2g3 , xenla-a0a1l8hdn0 , xenla-a0a1l8h622

Title : Characterization of a feruloyl esterase B from Talaromyces cellulolyticus - Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
Author(s) : Watanabe M , Yoshida E , Fukada H , Inoue H , Tokura M , Ishikawa K
Ref : Biosci Biotechnol Biochem , 79 :1845 , 2015
Abstract : A feruloyl esterase catalyzes the hydrolysis of the 4-hydroxy-3-methoxycinnamoyl (feruloyl) group from esterified sugars in plant cell walls. Talaromyces cellulolyticus is a high cellulolytic-enzyme producing fungus. However, there is no report for feruloyl esterase activity of T. cellulolyticus. Analysis of the genome database of T. cellulolyticus identified a gene encoding a putative feruloyl esterase B. The recombinant enzyme was prepared using a T. cellulolyticus homologous expression system and characterized. The purified enzyme exhibited hydrolytic activity toward p-nitrophenyl acetate, p-nitrophenyl trans-ferulate, methyl ferulate, rice husk, and bagasse. HPLC assays showed that the enzyme released ferulic acid and p-coumaric acid from hydrothermal-treated rice husk and bagasse. Trichoderma sp. is well-known high cellulolytic-enzyme producing fungus useful for the lignocellulosic biomass saccharification. Interestingly, no feruloyl esterase has been reported from Trichoderma sp. The results show that this enzyme is expected to be industrially useful for biomass saccharification.
ESTHER : Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
PubMedSearch : Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
PubMedID: 26110915
Gene_locus related to this paper: talce-faeB

Title : III-3 Dementia May Reduce the Ability of Low-Intensity Pulsed Ultrasound (LIPUS) to Accelerate Callus Formation in Elderly Female Patients With Trochanteric Fracture of the Femur - Watanabe_2015_J.Orthop.Trauma_29_S5
Author(s) : Watanabe M , Uchigashima H
Ref : J Orthop Trauma , 29 :S5 , 2015
Abstract : OBJECTIVE: Trochanteric fractures of the femur are common in elderly female patients with bone fragility, who frequently also have dementia. Some studies indicate that low-intensity pulsed ultrasound (LIPUS) accelerates callus formation in trochanteric fractures, but there have been few reports in patients with dementia. This retrospective study evaluated the effectiveness of LIPUS to accelerate callus formation in patients with trochanteric fracture and dementia. We also investigated the effect of acetylcholinesterase inhibitors (AChEIs), which are used to treat dementia, on LIPUS outcomes. PATIENTS AND
METHODS: Fifty-two hips of 51 elderly female patients with trochanteric fractures treated using the same intramedullary nail for proximal fixation were included. The appearance of callus was assessed by anteroposterior and lateral views on radiography. Dementia was evaluated using the revised Hasegawa's dementia scale (HDS-R), which has the validated cut-off of 20/21 to discriminate dementia from non-dementia.
RESULTS: In non-dementia patients without AChEI administration, the callus formation was observed significantly earlier in the LIPUS(+) group than in the LIPUS(-) group. In dementia patients without AChEI administration, there was no difference between the LIPUS(+) and LIPUS(-) groups. In dementia patients administered AChEI before the fracture, the callus formation was seen significantly earlier in the LIPUS(+) group compared with the LIPUS(-) group. DISCUSSION: The results indicate that, in the absence of AChEI administration, the effectiveness of LIPUS to accelerate the callus formation is likely reduced in elderly female patients with trochanteric fractures and dementia. However, LIPUS may accelerate callus formation, when combined with AChEI administration.
ESTHER : Watanabe_2015_J.Orthop.Trauma_29_S5
PubMedSearch : Watanabe_2015_J.Orthop.Trauma_29_S5
PubMedID: 25900762

Title : Identification of activating enzymes of a novel FBPase inhibitor prodrug, CS-917 - Kubota_2015_Pharmacol.Res.Perspect_3_e00138
Author(s) : Kubota K , Inaba S , Nakano R , Watanabe M , Sakurai H , Fukushima Y , Ichikawa K , Takahashi T , Izumi T , Shinagawa A
Ref : Pharmacol Res Perspect , 3 :e00138 , 2015
Abstract : CS-917 (MB06322) is a selective small compound inhibitor of fructose 1,6-bisphosphatase (FBPase), which is expected to be a novel drug for the treatment of type 2 diabetes by inhibiting gluconeogenesis. CS-917 is a bisamidate prodrug and activation of CS-917 requires a two-step enzyme catalyzed reaction. The first-step enzyme, esterase, catalyzes the conversion of CS-917 into the intermediate form (R-134450) and the second-step enzyme, phosphoramidase, catalyzes the conversion of R-134450 into the active form (R-125338). In this study, we biochemically purified the CS-917 esterase activity in monkey small intestine and liver. We identified cathepsin A (CTSA) and elastase 3B (ELA3B) as CS-917 esterases in the small intestine by mass spectrometry, whereas we found CTSA and carboxylesterase 1 (CES1) in monkey liver. We also purified R-134450 phosphoramidase activity in monkey liver and identified sphingomyelin phosphodiesterase, acid-like 3A (SMPADL3A), as an R-134450 phosphoramidase, which has not been reported to have any enzyme activity. Recombinant human CTSA, ELA3B, and CES1 showed CS-917 esterase activity and recombinant human SMPDL3A showed R-134450 phosphoramidase activity, which confirmed the identification of those enzymes. Identification of metabolic enzymes responsible for the activation process is the requisite first step to understanding the activation process, pharmacodynamics and pharmacokinetics of CS-917 at the molecular level. This is the first identification of a phosphoramidase other than histidine triad nucleotide-binding protein (HINT) family enzymes and SMPDL3A might generally contribute to activation of the other bisamidate prodrugs.
ESTHER : Kubota_2015_Pharmacol.Res.Perspect_3_e00138
PubMedSearch : Kubota_2015_Pharmacol.Res.Perspect_3_e00138
PubMedID: 26171222

Title : Crystal structure of an acetylesterase from Talaromyces cellulolyticus and the importance of a disulfide bond near the active site - Watanabe_2015_FEBS.Lett_589_1200
Author(s) : Watanabe M , Fukada H , Inoue H , Ishikawa K
Ref : FEBS Letters , 589 :1200 , 2015
Abstract : Carbohydrate esterase catalyzes the de-O or de-N-acylation of substituted saccharides in plant cell walls and thus has great potential for industrial biomass saccharification. We recently identified the putative carbohydrate esterase family 3 (CE3) from Talaromyces cellulolyticus. Here, we prepared the recombinant catalytic domain of the enzyme and crystallized it. The crystal structure was determined to 1.5A resolution. From the structural analysis, it was elucidated that a n-octyl-beta-d-glucopyranoside bound to near the catalytic triad (Ser10, Asp179 and His182) and was buried in the active site cavity. Site-directed mutagenesis showed that the N-terminal disulfide bond located near the catalytic triad is involved in the activity and structural stability of the enzyme.
ESTHER : Watanabe_2015_FEBS.Lett_589_1200
PubMedSearch : Watanabe_2015_FEBS.Lett_589_1200
PubMedID: 25825334

Title : Heterogeneous presynaptic distribution of monoacylglycerol lipase, a multipotent regulator of nociceptive circuits in the mouse spinal cord - Horvath_2014_Eur.J.Neurosci_39_419
Author(s) : Horvath E , Woodhams SG , Nyilas R , Henstridge CM , Kano M , Sakimura K , Watanabe M , Katona I
Ref : European Journal of Neuroscience , 39 :419 , 2014
Abstract : Monoacylglycerol lipase (MGL) is a multifunctional serine hydrolase, which terminates anti-nociceptive endocannabinoid signaling and promotes pro-nociceptive prostaglandin signaling. Accordingly, both acute nociception and its sensitization in chronic pain models are prevented by systemic or focal spinal inhibition of MGL activity. Despite its analgesic potential, the neurobiological substrates of beneficial MGL blockade have remained unexplored. Therefore, we examined the regional, cellular and subcellular distribution of MGL in spinal circuits involved in nociceptive processing. All immunohistochemical findings obtained with light, confocal or electron microscopy were validated in MGL-knockout mice. Immunoperoxidase staining revealed a highly concentrated accumulation of MGL in the dorsal horn, especially in superficial layers. Further electron microscopic analysis uncovered that the majority of MGL-immunolabeling is found in axon terminals forming either asymmetric glutamatergic or symmetric gamma-aminobutyric acid/glycinergic synapses in laminae I/IIo. In line with this presynaptic localization, analysis of double-immunofluorescence staining by confocal microscopy showed that MGL colocalizes with neurochemical markers of peptidergic and non-peptidergic nociceptive terminals, and also with markers of local excitatory or inhibitory interneurons. Interestingly, the ratio of MGL-immunolabeling was highest in calcitonin gene-related peptide-positive peptidergic primary afferents, and the staining intensity of nociceptive terminals was significantly reduced in MGL-knockout mice. These observations highlight the spinal nociceptor synapse as a potential anatomical site for the analgesic effects of MGL blockade. Moreover, the presence of MGL in additional terminal types raises the possibility that MGL may play distinct regulatory roles in synaptic endocannabinoid or prostaglandin signaling according to its different cellular locations in the dorsal horn pain circuitry.
ESTHER : Horvath_2014_Eur.J.Neurosci_39_419
PubMedSearch : Horvath_2014_Eur.J.Neurosci_39_419
PubMedID: 24494682

Title : Crystallization and preliminary X-ray crystallographic analysis of a putative feruloyl esterase from Talaromyces cellulolyticus - Watanabe_2014_Acta.Crystallogr.F.Struct.Biol.Commun_70_1664
Author(s) : Watanabe M , Ishikawa K
Ref : Acta Crystallographica F Struct Biol Commun , 70 :1664 , 2014
Abstract : Feruloyl esterase (FAE; EC 3.1.1.73) catalyzes the cleavage of the ester bond between ferulic acid and polysaccharides in plant cell walls, and thus holds significant potential for the industrial utilization of biomass saccharification. A feruloyl esterase was identified from the genome database of Talaromyces cellulolyticus (formerly known as Acremonium cellulolyticus). The gene consists of the catalytic domain and a carbohydrate-binding module connected through a serine/threonine-rich linker region. The recombinant enzyme was prepared, purified and crystallized at 293 K using 0.1 M imidazole pH 8.0, 0.2 M calcium acetate, 14% PEG 8000 as the precipitant. The crystal diffracted to 2.6 A resolution and the crystal system is primitive orthorhombic, with unit-cell parameters a = 90.9, b = 123.4, c = 135.4 A. Four molecules are assumed to be present per asymmetric unit, corresponding to a Matthews coefficient of 2.50 A(3) Da(-1) and a solvent content of 50.88%(v/v).
ESTHER : Watanabe_2014_Acta.Crystallogr.F.Struct.Biol.Commun_70_1664
PubMedSearch : Watanabe_2014_Acta.Crystallogr.F.Struct.Biol.Commun_70_1664
PubMedID: 25484222

Title : Klebsormidium flaccidum genome reveals primary factors for plant terrestrial adaptation - Hori_2014_Nat.Commun_5_3978
Author(s) : Hori K , Maruyama F , Fujisawa T , Togashi T , Yamamoto N , Seo M , Sato S , Yamada T , Mori H , Tajima N , Moriyama T , Ikeuchi M , Watanabe M , Wada H , Kobayashi K , Saito M , Masuda T , Sasaki-Sekimoto Y , Mashiguchi K , Awai K , Shimojima M , Masuda S , Iwai M , Nobusawa T , Narise T , Kondo S , Saito H , Sato R , Murakawa M , Ihara Y , Oshima-Yamada Y , Ohtaka K , Satoh M , Sonobe K , Ishii M , Ohtani R , Kanamori-Sato M , Honoki R , Miyazaki D , Mochizuki H , Umetsu J , Higashi K , Shibata D , Kamiya Y , Sato N , Nakamura Y , Tabata S , Ida S , Kurokawa K , Ohta H
Ref : Nat Commun , 5 :3978 , 2014
Abstract : The colonization of land by plants was a key event in the evolution of life. Here we report the draft genome sequence of the filamentous terrestrial alga Klebsormidium flaccidum (Division Charophyta, Order Klebsormidiales) to elucidate the early transition step from aquatic algae to land plants. Comparison of the genome sequence with that of other algae and land plants demonstrate that K. flaccidum acquired many genes specific to land plants. We demonstrate that K. flaccidum indeed produces several plant hormones and homologues of some of the signalling intermediates required for hormone actions in higher plants. The K. flaccidum genome also encodes a primitive system to protect against the harmful effects of high-intensity light. The presence of these plant-related systems in K. flaccidum suggests that, during evolution, this alga acquired the fundamental machinery required for adaptation to terrestrial environments.
ESTHER : Hori_2014_Nat.Commun_5_3978
PubMedSearch : Hori_2014_Nat.Commun_5_3978
PubMedID: 24865297
Gene_locus related to this paper: kleni-a0a1y1i5c5 , kleni-a0a1y1i3f9 , kleni-a0a1y1hnk2 , kleni-a0a1y1hsz2 , kleni-a0a1y1hva2 , kleni-a0a1y1i2g3 , kleni-a0a1y1i4h5 , kleni-a0a1y1i9h9

Title : Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses - Ishiura_2014_J.Hum.Genet_59_163
Author(s) : Ishiura H , Takahashi Y , Hayashi T , Saito K , Furuya H , Watanabe M , Murata M , Suzuki M , Sugiura A , Sawai S , Shibuya K , Ueda N , Ichikawa Y , Kanazawa I , Goto J , Tsuji S
Ref : J Hum Genet , 59 :163 , 2014
Abstract : Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP.
ESTHER : Ishiura_2014_J.Hum.Genet_59_163
PubMedSearch : Ishiura_2014_J.Hum.Genet_59_163
PubMedID: 24451228
Gene_locus related to this paper: human-SPG21

Title : Large splenic volume may be a useful predictor for partial splenic embolization-induced liver functional improvement in cirrhotic patients - Hayashi_2014_J.Hepatobiliary.Pancreat.Sci_21_51
Author(s) : Hayashi H , Beppu T , Masuda T , Okabe H , Imai K , Hashimoto D , Ikuta Y , Chikamoto A , Watanabe M , Baba H
Ref : J Hepatobiliary Pancreat Sci , 21 :51 , 2014
Abstract : BACKGROUND: Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients.
METHODS: From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count <10 x 10(4) /mul) underwent PSE. Of them, 71 patients with follow-up for more than one year after PSE were retrospectively investigated.
RESULTS: In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response. Indeed, serum albumin and cholinesterase levels increased to 104 +/- 14% and 130 +/- 65% each of the pretreatment level at one year after PSE. In a multiple linear regression analysis, preoperative splenic volume was extracted as the predictive factor for the improvement in cholinesterase level after PSE. Cirrhotic patients with preoperative splenic volume >600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). CONCLUSION: A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement.
ESTHER : Hayashi_2014_J.Hepatobiliary.Pancreat.Sci_21_51
PubMedSearch : Hayashi_2014_J.Hepatobiliary.Pancreat.Sci_21_51
PubMedID: 23798315

Title : Diacylglycerol lipase alpha manipulation reveals developmental roles for intercellular endocannabinoid signaling - Keimpema_2013_Sci.Rep_3_2093
Author(s) : Keimpema E , Alpar A , Howell F , Malenczyk K , Hobbs C , Hurd YL , Watanabe M , Sakimura K , Kano M , Doherty P , Harkany T
Ref : Sci Rep , 3 :2093 , 2013
Abstract : Endocannabinoids are small signaling lipids, with 2-arachidonoylglycerol (2-AG) implicated in modulating axonal growth and synaptic plasticity. The concept of short-range extracellular signaling by endocannabinoids is supported by the lack of trans-synaptic 2-AG signaling in mice lacking sn-1-diacylglycerol lipases (DAGLs), synthesizing 2-AG. Nevertheless, how far endocannabinoids can spread extracellularly to evoke physiological responses at CB(1) cannabinoid receptors (CB(1)Rs) remains poorly understood. Here, we first show that cholinergic innervation of CA1 pyramidal cells of the hippocampus is sensitive to the genetic disruption of 2-AG signaling in DAGLalpha null mice. Next, we exploit a hybrid COS-7-cholinergic neuron co-culture system to demonstrate that heterologous DAGLalpha overexpression spherically excludes cholinergic growth cones from 2-AG-rich extracellular environments, and minimizes cell-cell contact in vitro. CB(1)R-mediated exclusion responses lasted 3 days, indicating sustained spherical 2-AG availability. Overall, these data suggest that extracellular 2-AG concentrations can be sufficient to activate CB(1)Rs along discrete spherical boundaries to modulate neuronal responsiveness.
ESTHER : Keimpema_2013_Sci.Rep_3_2093
PubMedSearch : Keimpema_2013_Sci.Rep_3_2093
PubMedID: 23806960

Title : Activation of type 5 metabotropic glutamate receptors and diacylglycerol lipase-alpha initiates 2-arachidonoylglycerol formation and endocannabinoid-mediated analgesia - Gregg_2012_J.Neurosci_32_9457
Author(s) : Gregg LC , Jung KM , Spradley JM , Nyilas R , Suplita RL, 2nd , Zimmer A , Watanabe M , Mackie K , Katona I , Piomelli D , Hohmann AG
Ref : Journal of Neuroscience , 32 :9457 , 2012
Abstract : Acute stress reduces pain sensitivity by engaging an endocannabinoid signaling circuit in the midbrain. The neural mechanisms governing this process and molecular identity of the endocannabinoid substance(s) involved are unknown. We combined behavior, pharmacology, immunohistochemistry, RNA interference, quantitative RT-PCR, enzyme assays, and lipidomic analyses of endocannabinoid content to uncover the role of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) in controlling pain sensitivity in vivo. Here, we show that footshock stress produces antinociception in rats by activating type 5 metabotropic glutamate receptors (mGlu(5)) in the dorsolateral periaqueductal gray (dlPAG) and mobilizing 2-AG. Stimulation of mGlu(5) in the dlPAG with DHPG [(S)-3,5-dihydroxyphenylglycine] triggered 2-AG formation and enhanced stress-dependent antinociception through a mechanism dependent upon both postsynaptic diacylglycerol lipase (DGL) activity, which releases 2-AG, and presynaptic CB(1) cannabinoid receptors. Pharmacological blockade of DGL activity in the dlPAG with RHC80267 [1,6-bis(cyclohexyloximinocarbonylamino)hexane] and (-)-tetrahydrolipstatin (THL), which inhibit activity of DGL-alpha and DGL-beta isoforms, suppressed stress-induced antinociception. Inhibition of DGL activity in the dlPAG with THL selectively decreased accumulation of 2-AG without altering levels of anandamide. The putative 2-AG-synthesizing enzyme DGL-alpha colocalized with mGlu(5) at postsynaptic sites of the dlPAG, whereas CB(1) was confined to presynaptic terminals, consistent with a role for 2-AG as a retrograde signaling messenger. Finally, virally mediated silencing of DGL-alpha, but not DGL-beta, transcription in the dlPAG mimicked effects of DGL inhibition in suppressing both endocannabinoid-mediated stress antinociception and 2-AG formation. The results indicate that activation of the postsynaptic mGlu(5)-DGL-alpha cascade triggers retrograde 2-AG signaling in vivo. This pathway is required for endocannabinoid-mediated stress-induced analgesia.
ESTHER : Gregg_2012_J.Neurosci_32_9457
PubMedSearch : Gregg_2012_J.Neurosci_32_9457
PubMedID: 22787031
Gene_locus related to this paper: human-DAGLA

Title : Lack of molecular-anatomical evidence for GABAergic influence on axon initial segment of cerebellar Purkinje cells by the pinceau formation - Iwakura_2012_J.Neurosci_32_9438
Author(s) : Iwakura A , Uchigashima M , Miyazaki T , Yamasaki M , Watanabe M
Ref : Journal of Neuroscience , 32 :9438 , 2012
Abstract : The axon initial segment (AIS) of cerebellar Purkinje cells (PCs) is embraced by ramified axons of GABAergic basket cells (BCs) called the pinceau formation. This unique structure has been assumed to be a device for the modulation of PC outputs through electrical and/or GABAergic inhibition. Electrical inhibition is supported by enriched potassium channels, absence of sodium channels, and developed septate-like junctions between BC axons. The neurochemical basis for GABAergic inhibition, however, has not been well investigated. Here we addressed this issue using C56BL/6 mice. First, we confirmed previous observations that typical synaptic contacts were rare and confined to proximal axonal portions, with the remaining portions being mostly covered by astrocytic processes. Then we examined the expression of molecules involved in GABAergic signaling, including GABA synthetic enzyme glutamic acid decarboxylase (GAD), vesicular GABA transporter vesicular inhibitory amino acid transporter (VIAAT), cytomatrix active zone protein bassoon, GABA receptor GABA(A)Ralpha1, and cell adhesion molecule neuroligin-2. These molecules were recruited to form a functional assembly at perisomatic BC-PC synapses and along the AIS of hippocampal and neocortical pyramidal cells. GAD and VIAAT immunogold labeling was five times lower in the pinceau formation compared with perisomatic BC terminals and showed no accumulation toward the AIS. Moreover, bassoon, neuroligin-2, and GABA(A)Ralpha1 formed no detectable clusters along the ankyrin-G-positive AIS proper. These findings indicate that GABAergic signaling machinery is organized loosely and even incompletely in the pinceau formation. Together, BCs do not appear to exert GABAergic synaptic inhibition on the AIS, although the mode of action of the pinceau formation remains to be explored.
ESTHER : Iwakura_2012_J.Neurosci_32_9438
PubMedSearch : Iwakura_2012_J.Neurosci_32_9438
PubMedID: 22764252

Title : Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium - Matsumoto_2012_PLoS.One_7_e42841
Author(s) : Matsumoto H , Shibasaki K , Uchigashima M , Koizumi A , Kurachi M , Moriwaki Y , Misawa H , Kawashima K , Watanabe M , Kishi S , Ishizaki Y
Ref : PLoS ONE , 7 :e42841 , 2012
Abstract : It has been long speculated that specific signals are transmitted from photoreceptors to the retinal pigment epithelium (RPE). However, such signals have not been identified. In this study, we examined the retinal expression and localization of acetylcholine-related molecules as putative candidates for these signals. Previous reports revealed that alpha7 nicotinic acetylcholine receptors (nAChRs) are present in the microvilli of RPE cells that envelope the tips of photoreceptor outer segments (OS). Secreted mammalian leukocyte antigen 6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) is a positive allosteric modulator of the alpha7 nAChR. Therefore, we first focused on the expression of SLURP-1. SLURP-1 mRNA was expressed in the outer nuclear layer, which is comprised of photoreceptor cell bodies. SLURP-1 immunoreactivity co-localized with rhodopsin and S-opsin in photoreceptor OS, while choline acetyltransferase (ChAT) and high affinity choline transporter (CHT-1) were also expressed in photoreceptor OS. Immunoelectron microscopy identified that the majority of SLURP-1 was localized to the plasma membranes of photoreceptor OS. These results provide evidence that SLURP-1 is synthesized in photoreceptor cell bodies and transported to photoreceptor OS, where SLURP-1 may also be secreted. Our findings suggest that photoreceptor OS communicate via neurotransmitters such as ACh and SLURP-1, while RPE cells might receive these signals through alpha7 nAChRs in their microvilli.
ESTHER : Matsumoto_2012_PLoS.One_7_e42841
PubMedSearch : Matsumoto_2012_PLoS.One_7_e42841
PubMedID: 22880119

Title : Molecular reorganization of endocannabinoid signalling in Alzheimer's disease - Mulder_2011_Brain_134_1041
Author(s) : Mulder J , Zilberter M , Pasquare SJ , Alpar A , Schulte G , Ferreira SG , Kofalvi A , Martin-Moreno AM , Keimpema E , Tanila H , Watanabe M , Mackie K , Hortobagyi T , de Ceballos ML , Harkany T
Ref : Brain , 134 :1041 , 2011
Abstract : Retrograde messengers adjust the precise timing of neurotransmitter release from the presynapse, thus modulating synaptic efficacy and neuronal activity. 2-Arachidonoyl glycerol, an endocannabinoid, is one such messenger produced in the postsynapse that inhibits neurotransmitter release upon activating presynaptic CB(1) cannabinoid receptors. Cognitive decline in Alzheimer's disease is due to synaptic failure in hippocampal neuronal networks. We hypothesized that errant retrograde 2-arachidonoyl glycerol signalling impairs synaptic neurotransmission in Alzheimer's disease. Comparative protein profiling and quantitative morphometry showed that overall CB(1) cannabinoid receptor protein levels in the hippocampi of patients with Alzheimer's disease remain unchanged relative to age-matched controls, and CB(1) cannabinoid receptor-positive presynapses engulf amyloid-beta-containing senile plaques. Hippocampal protein concentrations for the sn-1-diacylglycerol lipase alpha and beta isoforms, synthesizing 2-arachidonoyl glycerol, significantly increased in definite Alzheimer's (Braak stage VI), with ectopic sn-1-diacylglycerol lipase beta expression found in microglia accumulating near senile plaques and apposing CB(1) cannabinoid receptor-positive presynapses. We found that microglia, expressing two 2-arachidonoyl glycerol-degrading enzymes, serine hydrolase alpha/beta-hydrolase domain-containing 6 and monoacylglycerol lipase, begin to surround senile plaques in probable Alzheimer's disease (Braak stage III). However, Alzheimer's pathology differentially impacts serine hydrolase alpha/beta-hydrolase domain-containing 6 and monoacylglycerol lipase in hippocampal neurons: serine hydrolase alpha/beta-hydrolase domain-containing 6 expression ceases in neurofibrillary tangle-bearing pyramidal cells. In contrast, pyramidal cells containing hyperphosphorylated tau retain monoacylglycerol lipase expression, although at levels significantly lower than in neurons lacking neurofibrillary pathology. Here, monoacylglycerol lipase accumulates in CB(1) cannabinoid receptor-positive presynapses. Subcellular fractionation revealed impaired monoacylglycerol lipase recruitment to biological membranes in post-mortem Alzheimer's tissues, suggesting that disease progression slows the termination of 2-arachidonoyl glycerol signalling. We have experimentally confirmed that altered 2-arachidonoyl glycerol signalling could contribute to synapse silencing in Alzheimer's disease by demonstrating significantly prolonged depolarization-induced suppression of inhibition when superfusing mouse hippocampi with amyloid-beta. We propose that the temporal dynamics and cellular specificity of molecular rearrangements impairing 2-arachidonoyl glycerol availability and actions may differ from those of anandamide. Thus, enhanced endocannabinoid signalling, particularly around senile plaques, can exacerbate synaptic failure in Alzheimer's disease.
ESTHER : Mulder_2011_Brain_134_1041
PubMedSearch : Mulder_2011_Brain_134_1041
PubMedID: 21459826

Title : Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus - Ludanyi_2011_Neurosci_174_50
Author(s) : Ludanyi A , Hu SS , Yamazaki M , Tanimura A , Piomelli D , Watanabe M , Kano M , Sakimura K , Magloczky Z , Mackie K , Freund TF , Katona I
Ref : Neuroscience , 174 :50 , 2011
Abstract : Clinical and experimental evidence demonstrates that endocannabinoids play either beneficial or adverse roles in many neurological and psychiatric disorders. Their medical significance may be best explained by the emerging concept that endocannabinoids are essential modulators of synaptic transmission throughout the central nervous system. However, the precise molecular architecture of the endocannabinoid signaling machinery in the human brain remains elusive. To address this issue, we investigated the synaptic distribution of metabolic enzymes for the most abundant endocannabinoid molecule, 2-arachidonoylglycerol (2-AG), in the postmortem human hippocampus. Immunostaining for diacylglycerol lipase-alpha (DGL-alpha), the main synthesizing enzyme of 2-AG, resulted in a laminar pattern corresponding to the termination zones of glutamatergic pathways. The highest density of DGL-alpha-immunostaining was observed in strata radiatum and oriens of the cornu ammonis and in the inner third of stratum moleculare of the dentate gyrus. At higher magnification, DGL-alpha-immunopositive puncta were distributed throughout the neuropil outlining the immunonegative main dendrites of pyramidal and granule cells. Electron microscopic analysis revealed that this pattern was due to the accumulation of DGL-alpha in dendritic spine heads. Similar DGL-alpha-immunostaining pattern was also found in hippocampi of wild-type, but not of DGL-alpha knockout mice. Using two independent antibodies developed against monoacylglycerol lipase (MGL), the predominant enzyme inactivating 2-AG, immunostaining also revealed a laminar and punctate staining pattern. However, as observed previously in rodent hippocampus, MGL was enriched in axon terminals instead of postsynaptic structures at the ultrastructural level. Taken together, these findings demonstrate the post- and presynaptic segregation of primary enzymes responsible for synthesis and elimination of 2-AG, respectively, in the human hippocampus. Thus, molecular architecture of the endocannabinoid signaling machinery supports retrograde regulation of synaptic activity, and its similar blueprint in rodents and humans further indicates that 2-AG's physiological role as a negative feed-back signal is an evolutionarily conserved feature of excitatory synapses.
ESTHER : Ludanyi_2011_Neurosci_174_50
PubMedSearch : Ludanyi_2011_Neurosci_174_50
PubMedID: 21035522

Title : The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission - Tanimura_2010_Neuron_65_320
Author(s) : Tanimura A , Yamazaki M , Hashimotodani Y , Uchigashima M , Kawata S , Abe M , Kita Y , Hashimoto K , Shimizu T , Watanabe M , Sakimura K , Kano M
Ref : Neuron , 65 :320 , 2010
Abstract : Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains, whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha, but not by DGLbeta, mediates retrograde suppression at central synapses.
ESTHER : Tanimura_2010_Neuron_65_320
PubMedSearch : Tanimura_2010_Neuron_65_320
PubMedID: 20159446
Gene_locus related to this paper: human-DAGLA

Title : Retrograde endocannabinoid signaling reduces GABAergic synaptic transmission to gonadotropin-releasing hormone neurons - Farkas_2010_Endocrinology_151_5818
Author(s) : Farkas I , Kallo I , Deli L , Vida B , Hrabovszky E , Fekete C , Moenter SM , Watanabe M , Liposits Z
Ref : Endocrinology , 151 :5818 , 2010
Abstract : Cannabinoids suppress fertility via reducing hypothalamic GnRH output. gamma-Aminobutyric acid (GABA)(A) receptor (GABA(A)-R)-mediated transmission is a major input to GnRH cells that can be excitatory. We hypothesized that cannabinoids act via inhibiting GABAergic input. We performed loose-patch electrophysiological studies of acute slices from adult male GnRH-green fluorescent protein transgenic mice. Bath application of type 1 cannabinoid receptor (CB1) agonist WIN55,212 decreased GnRH neuron firing rate. This action was detectable in presence of the glutamate receptor antagonist kynurenic acid but disappeared when bicuculline was also present, indicating GABA(A)-R involvement. In immunocytochemical experiments, CB1-immunoreactive axons formed contacts with GnRH neurons and a subset established symmetric synapses characteristic of GABAergic neurotransmission. Functional studies were continued with whole-cell patch-clamp electrophysiology in presence of tetrodotoxin. WIN55,212 decreased the frequency of GABA(A)-R-mediated miniature postsynaptic currents (mPSCs) (reflecting spontaneous vesicle fusion), which was prevented with the CB1 antagonist AM251, indicating collectively that activation of presynaptic CB1 inhibits GABA release. AM251 alone increased mPSC frequency, providing evidence that endocannabinoids tonically inhibit GABA(A)-R drive onto GnRH neurons. Increased mPSC frequency was absent when diacylglycerol lipase was blocked intracellularly with tetrahydrolipstatin, showing that tonic inhibition is caused by 2-arachidonoylglycerol production of GnRH neurons. CdCl(2) in extracellular solution can maintain both action potentials and spontaneous vesicle fusion. Under these conditions, when endocannabinoid-mediated blockade of spontaneous vesicle fusion was blocked with AM251, GnRH neuron firing increased, revealing an endogenous endocannabinoid brake on GnRH neuron firing. Retrograde endocannabinoid signaling may represent an important mechanism under physiological and pathological conditions whereby GnRH neurons regulate their excitatory GABAergic inputs.
ESTHER : Farkas_2010_Endocrinology_151_5818
PubMedSearch : Farkas_2010_Endocrinology_151_5818
PubMedID: 20926585

Title : Differential subcellular recruitment of monoacylglycerol lipase generates spatial specificity of 2-arachidonoyl glycerol signaling during axonal pathfinding - Keimpema_2010_J.Neurosci_30_13992
Author(s) : Keimpema E , Barabas K , Morozov YM , Tortoriello G , Torii M , Cameron G , Yanagawa Y , Watanabe M , Mackie K , Harkany T
Ref : Journal of Neuroscience , 30 :13992 , 2010
Abstract : Endocannabinoids, particularly 2-arachidonoyl glycerol (2-AG), impact the directional turning and motility of a developing axon by activating CB(1) cannabinoid receptors (CB(1)Rs) in its growth cone. Recent findings posit that sn-1-diacylglycerol lipases (DAGLalpha/beta) synthesize 2-AG in the motile axon segment of developing pyramidal cells. Coincident axonal targeting of CB(1)Rs and DAGLs prompts the hypothesis that autocrine 2-AG signaling facilitates axonal outgrowth. However, DAGLs alone are insufficient to account for the spatial specificity and dynamics of 2-AG signaling. Therefore, we hypothesized that local 2-AG degradation by monoacylglycerol lipase (MGL) must play a role. We determined how subcellular recruitment of MGL is temporally and spatially restricted to establish the signaling competence of 2-AG during axonal growth. MGL is expressed in central and peripheral axons of the fetal nervous system by embryonic day 12.5. MGL coexists with DAGLalpha and CB(1)Rs in corticofugal axons of pyramidal cells. Here, MGL and DAGLalpha undergo differential axonal targeting with MGL being excluded from the motile neurite tip. Thus, spatially confined MGL activity generates a 2-AG-sensing microdomain and configures 2-AG signaling to promote axonal growth. Once synaptogenesis commences, MGL disperses in stationary growth cones. The axonal polarity of MGL is maintained by differential proteasomal degradation because inhibiting the ubiquitin proteasome system also induces axonal MGL redistribution. Because MGL inactivation drives a CB(1)R-dependent axonal growth response, we conclude that 2-AG may act as a focal protrusive signal for developing neurons and whose regulated metabolism is critical for attaining correct axonal complexity.
ESTHER : Keimpema_2010_J.Neurosci_30_13992
PubMedSearch : Keimpema_2010_J.Neurosci_30_13992
PubMedID: 20962221

Title : Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors - Shin_2009_J.Neurosci_29_15375
Author(s) : Shin J , Gireesh G , Kim SW , Kim DS , Lee S , Kim YS , Watanabe M , Shin HS
Ref : Journal of Neuroscience , 29 :15375 , 2009
Abstract : Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.
ESTHER : Shin_2009_J.Neurosci_29_15375
PubMedSearch : Shin_2009_J.Neurosci_29_15375
PubMedID: 20007462

Title : Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether biosynthesis - Shichijo_2008_J.Am.Chem.Soc_130_12230
Author(s) : Shichijo Y , Migita A , Oguri H , Watanabe M , Tokiwano T , Watanabe K , Oikawa H
Ref : Journal of the American Chemical Society , 130 :12230 , 2008
Abstract : Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.
ESTHER : Shichijo_2008_J.Am.Chem.Soc_130_12230
PubMedSearch : Shichijo_2008_J.Am.Chem.Soc_130_12230
PubMedID: 18710235

Title : Synapse formation and clustering of neuroligin-2 in the absence of GABAA receptors - Patrizi_2008_Proc.Natl.Acad.Sci.U.S.A_105_13151
Author(s) : Patrizi A , Scelfo B , Viltono L , Briatore F , Fukaya M , Watanabe M , Strata P , Varoqueaux F , Brose N , Fritschy JM , Sassoe-Pognetto M
Ref : Proc Natl Acad Sci U S A , 105 :13151 , 2008
Abstract : GABAergic synapses are crucial for brain function, but the mechanisms underlying inhibitory synaptogenesis are unclear. Here, we show that postnatal Purkinje cells (PCs) of GABA(A)alpha1 knockout (KO) mice express transiently the alpha3 subunit, leading to the assembly of functional GABA(A) receptors and initial normal formation of inhibitory synapses, that are retained until adulthood. Subsequently, down-regulation of the alpha3 subunit causes a complete loss of GABAergic postsynaptic currents, resulting in a decreased rate of inhibitory synaptogenesis and formation of mismatched synapses between GABAergic axons and PC spines. Notably, the postsynaptic adhesion molecule neuroligin-2 (NL2) is correctly targeted to inhibitory synapses lacking GABA(A) receptors and the scaffold molecule gephyrin, but is absent from mismatched synapses, despite innervation by GABAergic axons. Our data indicate that GABA(A) receptors are dispensable for synapse formation and maintenance and for targeting NL2 to inhibitory synapses. However, GABAergic signaling appears to be crucial for activity-dependent regulation of synapse density during neuronal maturation.
ESTHER : Patrizi_2008_Proc.Natl.Acad.Sci.U.S.A_105_13151
PubMedSearch : Patrizi_2008_Proc.Natl.Acad.Sci.U.S.A_105_13151
PubMedID: 18723687

Title : Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus - Ludanyi_2008_J.Neurosci_28_2976
Author(s) : Ludanyi A , Eross L , Czirjak S , Vajda J , Halasz P , Watanabe M , Palkovits M , Magloczky Z , Freund TF , Katona I
Ref : Journal of Neuroscience , 28 :2976 , 2008
Abstract : Endocannabinoid signaling is a key regulator of synaptic neurotransmission throughout the brain. Compelling evidence shows that its perturbation leads to development of epileptic seizures, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. To elucidate whether long-term reorganization of endocannabinoid signaling occurs in epileptic patients, we performed comparative expression profiling along with quantitative electron microscopic analysis in control (postmortem samples from subjects with no signs of neurological disorders) and epileptic (surgically removed from patients with intractable temporal lobe epilepsy) hippocampal tissue. Quantitative PCR measurements revealed that CB(1) cannabinoid receptor mRNA was downregulated to one-third of its control value in epileptic hippocampus. Likewise, the cannabinoid receptor-interacting protein-1a mRNA was decreased, whereas 1b isoform levels were unaltered. Expression of diacylglycerol lipase-alpha, an enzyme responsible for 2-arachidonoylglycerol synthesis, was also reduced by approximately 60%, whereas its related beta isoform levels were unchanged. Expression level of N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, metabolic enzymes of anandamide, and 2-arachidonoylglycerol's degrading enzyme monoacylglycerol lipase did not change. The density of CB(1) immunolabeling was also decreased in epileptic hippocampus, predominantly in the dentate gyrus, where quantitative electron microscopic analysis did not reveal changes in the ratio of CB(1)-positive GABAergic boutons, but uncovered robust reduction in the fraction of CB(1)-positive glutamatergic axon terminals. These findings show that a neuroprotective machinery involving endocannabinoids is impaired in epileptic human hippocampus and imply that downregulation of CB(1) receptors and related molecular components of the endocannabinoid system may facilitate the deleterious effects of increased network excitability.
ESTHER : Ludanyi_2008_J.Neurosci_28_2976
PubMedSearch : Ludanyi_2008_J.Neurosci_28_2976
PubMedID: 18354002

Title : Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor - Yoshida_2006_J.Neurosci_26_4740
Author(s) : Yoshida T , Fukaya M , Uchigashima M , Miura E , Kamiya H , Kano M , Watanabe M
Ref : Journal of Neuroscience , 26 :4740 , 2006
Abstract : 2-arachidonoyl-glycerol (2-AG) is an endocannabinoid that is released from postsynaptic neurons, acts retrogradely on presynaptic cannabinoid receptor CB1, and induces short- and long-term suppression of transmitter release. To understand the mechanisms of the 2-AG-mediated retrograde modulation, we investigated subcellular localization of a major 2-AG biosynthetic enzyme, diacylglycerol lipase-alpha (DAGLalpha), by using immunofluorescence and immunoelectron microscopy in the mouse brain. In the cerebellum, DAGLalpha was predominantly expressed in Purkinje cells. DAGLalpha was detected on the dendritic surface and occasionally on the somatic surface, with a distal-to-proximal gradient from spiny branchlets toward somata. DAGLalpha was highly concentrated at the base of spine neck and also accumulated with much lower density on somatodendritic membrane around the spine neck. However, DAGLalpha was excluded from the main body of spine neck and head. In hippocampal pyramidal cells, DAGLalpha was also accumulated in spines. In contrast to the distribution in Purkinje cells, DAGLalpha was distributed in the spine head, neck, or both, whereas somatodendritic membrane was labeled very weakly. These results indicate that DAGLalpha is essentially targeted to postsynaptic spines in cerebellar and hippocampal neurons, but its fine distribution within and around spines is differently regulated between the two neurons. The preferential spine targeting should enable efficient 2-AG production on excitatory synaptic activity and its swift retrograde modulation onto nearby presynaptic terminals expressing CB1. Furthermore, different fine localization within and around spines suggests that the distance between postsynaptic 2-AG production site and presynaptic CB1 is differentially controlled depending on neuron types.
ESTHER : Yoshida_2006_J.Neurosci_26_4740
PubMedSearch : Yoshida_2006_J.Neurosci_26_4740
PubMedID: 16672646

Title : Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non-responsive to interferon therapy - Hamamoto_2005_J.Gastroenterol.Hepatol_20_204
Author(s) : Hamamoto S , Uchida Y , Wada T , Moritani M , Sato S , Hamamoto N , Ishihara S , Watanabe M , Kinoshita Y
Ref : J Gastroenterol Hepatol , 20 :204 , 2005
Abstract : BACKGROUND: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non-responders to treatment.
METHODS: In total, 101 patients with chronic HCV positive hepatitis were enrolled in this study. High dose interferon alpha was given on alternate days for 6 months. Six months after the end of treatment patients were assessed for the presence or absence of HCV RNA to determine the results of interferon treatment. The time courses of changes in serum lipid concentrations were measured in all patients.
RESULTS: The total cholesterol level increased gradually during and after interferon therapy, and its pattern of change coincided with that of serum cholinesterase activity. Pretreatment serum cholesterol concentrations did not differ between responders and non-responders to interferon therapy. The serum triglyceride concentration, conversely, showed a sharp increase during interferon administration and returned to its basal level after the end of treatment. Responders to interferon therapy tended to have higher pretreatment triglyceride concentrations than did non-responders.
CONCLUSIONS: We clarified that serum cholesterol and triglyceride levels showed different patterns of change during interferon therapy.
ESTHER : Hamamoto_2005_J.Gastroenterol.Hepatol_20_204
PubMedSearch : Hamamoto_2005_J.Gastroenterol.Hepatol_20_204
PubMedID: 15683422

Title : Complete sequencing and characterization of 21,243 full-length human cDNAs - Ota_2004_Nat.Genet_36_40
Author(s) : Ota T , Suzuki Y , Nishikawa T , Otsuki T , Sugiyama T , Irie R , Wakamatsu A , Hayashi K , Sato H , Nagai K , Kimura K , Makita H , Sekine M , Obayashi M , Nishi T , Shibahara T , Tanaka T , Ishii S , Yamamoto J , Saito K , Kawai Y , Isono Y , Nakamura Y , Nagahari K , Murakami K , Yasuda T , Iwayanagi T , Wagatsuma M , Shiratori A , Sudo H , Hosoiri T , Kaku Y , Kodaira H , Kondo H , Sugawara M , Takahashi M , Kanda K , Yokoi T , Furuya T , Kikkawa E , Omura Y , Abe K , Kamihara K , Katsuta N , Sato K , Tanikawa M , Yamazaki M , Ninomiya K , Ishibashi T , Yamashita H , Murakawa K , Fujimori K , Tanai H , Kimata M , Watanabe M , Hiraoka S , Chiba Y , Ishida S , Ono Y , Takiguchi S , Watanabe S , Yosida M , Hotuta T , Kusano J , Kanehori K , Takahashi-Fujii A , Hara H , Tanase TO , Nomura Y , Togiya S , Komai F , Hara R , Takeuchi K , Arita M , Imose N , Musashino K , Yuuki H , Oshima A , Sasaki N , Aotsuka S , Yoshikawa Y , Matsunawa H , Ichihara T , Shiohata N , Sano S , Moriya S , Momiyama H , Satoh N , Takami S , Terashima Y , Suzuki O , Nakagawa S , Senoh A , Mizoguchi H , Goto Y , Shimizu F , Wakebe H , Hishigaki H , Watanabe T , Sugiyama A , Takemoto M , Kawakami B , Watanabe K , Kumagai A , Itakura S , Fukuzumi Y , Fujimori Y , Komiyama M , Tashiro H , Tanigami A , Fujiwara T , Ono T , Yamada K , Fujii Y , Ozaki K , Hirao M , Ohmori Y , Kawabata A , Hikiji T , Kobatake N , Inagaki H , Ikema Y , Okamoto S , Okitani R , Kawakami T , Noguchi S , Itoh T , Shigeta K , Senba T , Matsumura K , Nakajima Y , Mizuno T , Morinaga M , Sasaki M , Togashi T , Oyama M , Hata H , Komatsu T , Mizushima-Sugano J , Satoh T , Shirai Y , Takahashi Y , Nakagawa K , Okumura K , Nagase T , Nomura N , Kikuchi H , Masuho Y , Yamashita R , Nakai K , Yada T , Ohara O , Isogai T , Sugano S
Ref : Nat Genet , 36 :40 , 2004
Abstract : As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.
ESTHER : Ota_2004_Nat.Genet_36_40
PubMedSearch : Ota_2004_Nat.Genet_36_40
PubMedID: 14702039
Gene_locus related to this paper: human-ABHD1 , human-ABHD4 , human-ABHD12 , human-ABHD16A , human-ACOT1 , human-LDAH , human-ABHD18 , human-CES1 , human-CES4A , human-CES5A , human-CPVL , human-DAGLB , human-EPHX2 , human-KANSL3 , human-LIPA , human-LPL , human-MEST , human-NDRG1 , human-NLGN1 , human-NLGN4X , human-PRCP , human-PRSS16 , human-SERAC1 , human-TMEM53

Title : Biliary indocyanine green excretion as a predictor of hepatic adenosine triphosphate levels in patients with obstructive jaundice - Chijiiwa_2000_Am.J.Surg_179_161
Author(s) : Chijiiwa K , Watanabe M , Nakano K , Noshiro H , Tanaka M
Ref : American Journal of Surgery , 179 :161 , 2000
Abstract : BACKGROUND: Correlation of the hepatic adenosine triphosphate (ATP) level with indocyanine green (ICG) excretion into bile was examined in patients with obstructive jaundice after the relief of hyperbilirubinemia by preoperative percutaneous transhepatic biliary drainage (PTBD).
METHODS: Patients with complete bile duct obstruction, the mean serum total bilirubin concentration being 13.6 +/- 8.5 (SD) mg/dL, underwent PTBD prior to surgery. Within a few days before surgery when the mean serum total bilirubin level decreased to 1.2 mg/dL, ICG (0.5 mg/kg) was intravenously injected, and the whole bile was collected at 1-hour intervals for 5 hours. The ICG concentration in bile, bile flow rate, amount of ICG excreted in bile, and biliary ICG excretion rate as percentage of the injected dose were determined. At the time of surgery, a small liver tissue sample was obtained immediately after laparotomy without any ischemic procedures, and ATP concentrations were determined. Results of hepatic ATP levels were correlated with laboratory and clinical determinations.
RESULTS: The bile flow rate was essentially constant during the 5-hour period, the mean value being 21 mL/hour. The ICG concentrations in bile gradually increased, reached the maximal level in 3 hour, and declined thereafter. The biliary ICG excretion rate for 5 hours was 40% +/- 18% of its injected dose. The biliary ICG excretion rate and amount of ICG excreted in bile for 5 hours significantly (P <0.05) correlated with the hepatic ATP level. The decline index of serum bilirubin during PTBD was also correlated with the hepatic ATP level. The serum ICG retention rate, bile flow rate, maximal ICG concentration in bile, and other liver function tests including serum albumin and cholinesterase levels did not correlate with the hepatic ATP level.
CONCLUSIONS: Both the amount of and excretion rate of ICG in bile reflect the hepatic ATP level. Determination of biliary ICG excretion contributes to precise evaluation of hepatic energy status before surgery in patients with obstructive jaundice.
ESTHER : Chijiiwa_2000_Am.J.Surg_179_161
PubMedSearch : Chijiiwa_2000_Am.J.Surg_179_161
PubMedID: 10773154

Title : Quantal ATP release from motor nerve endings and its role in neurally mediated depression -
Author(s) : Silinsky EM , Hirsh JK , Searl TJ , Redman RS , Watanabe M
Ref : Prog Brain Res , 120 :145 , 1999
PubMedID: 10550994

Title : Molecular cloning of cDNAs encoding alpha1, alpha2, and beta subunits of rat brain platelet-activating factor acetylhydrolase - Watanabe_1998_Biochim.Biophys.Acta_1401_73
Author(s) : Watanabe M , Aoki J , Manya H , Arai H , Inoue K
Ref : Biochimica & Biophysica Acta , 1401 :73 , 1998
Abstract : Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH(Ib)) is a tertiary G-protein-complex-like heterotrimeric enzyme which is composed of alpha1, alpha2, and beta subunits and is implicated in stages of brain development such as the formation of the brain cortex. We have isolated and sequenced cDNA clones encoding these three subunits of rat brain PAF-AH(Ib). The amino acid sequences of brain PAF-AH has shown an extremely high homology among mammalian species. The tissue distribution of the three subunits was examined by Northern blot analysis. Although the mRNAs were detected in various organs, the ratio of the level of mRNA expression for the three subunits differed among rat tissues, raising the possibility that isoform(s) other than the heterotrimeric isoform exist in certain tissues.
ESTHER : Watanabe_1998_Biochim.Biophys.Acta_1401_73
PubMedSearch : Watanabe_1998_Biochim.Biophys.Acta_1401_73
PubMedID: 9459487

Title : Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain - Manya_1998_J.Biol.Chem_273_18567
Author(s) : Manya H , Aoki J , Watanabe M , Adachi T , Asou H , Inoue Y , Arai H , Inoue K
Ref : Journal of Biological Chemistry , 273 :18567 , 1998
Abstract : In a previous study, we demonstrated that Platelet-activating Factor (PAF) acetylhydrolase purified from bovine brain cortical cytosol consists of two mutually homologous catalytic subunits (alpha1 and alpha2) and one putative regulatory beta subunit. The latter is a product of the LIS1 gene, which is defective in the Miller-Dieker syndrome, a form of lissencephaly. In this study, we examined the expression patterns of these three subunits in the developing rat brain. All three subunits were expressed in embryonic brain, whereas only alpha2 and beta subunit were detected in the adult brain by Western blotting. Biochemical analyses revealed that the alpha1/alpha2 heterodimer and alpha2/alpha2 homodimer are major catalytic units of embryonic and adult brain PAF acetylhydrolases, respectively. The alpha1 transcript and protein were detected predominantly in embryonic and postnatal neural tissues, such as the brain and spinal cord. Furthermore, we found using primary cultured cells isolated from neonatal rat brain that alpha1 protein were expressed only in neurons but not in glial cells and fibroblasts. In contrast, alpha2 and beta transcripts and proteins were detected both in neural and non-neural tissues, and their expression level was almost constant from fetal stages through adulthood. These results indicate that alpha1 expression is restricted to actively migrating neurons in rats and that switching of catalytic subunits from the alpha1/alpha2 heterodimer to the alpha2/alpha2 homodimer occurred in these cells during brain development, suggesting that PAF acetylhydrolase plays a role(s) in neuronal migration.
ESTHER : Manya_1998_J.Biol.Chem_273_18567
PubMedSearch : Manya_1998_J.Biol.Chem_273_18567
PubMedID: 9660828

Title : Oxo-type organophosphate-resistant acetylcholinesterase from organophosphate-unsusceptible Culex tritaeniorhynchus -
Author(s) : Watanabe M , Takebe S , Kim DH , Arakawa R , Kamimura K , Kobashi K
Ref : Chem Pharm Bull (Tokyo) , 36 :312 , 1988
PubMedID: 3378294

Title : The distribution of NCAM in the chick hindlimb during axon outgrowth and synaptogenesis - Tosney_1986_Dev.Biol_114_437
Author(s) : Tosney KW , Watanabe M , Landmesser L , Rutishauser U
Ref : Developmental Biology , 114 :437 , 1986
Abstract : We have determined the distribution and form of the neural cell adhesion molecule (NCAM) in the chick hindlimb from initial axon outgrowth (stage 17 1/2) until 3 days posthatching by immunohistological staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots. Axons stained intensely for NCAM at all ages, whereas nonneuronal limb components exhibited dynamic changes in staining. Mesenchymal cells in the sclerotome adjacent to the neural tube developed NCAM immunoreactivity in an anterior-posterior sequence which correlated with the sequence of axonal outgrowth. Low to moderate amounts of NCAM were detected within and surrounding presumptive nerve pathways, consistent with a permissive role for NCAM in axon extension, but not with a precise delineation of pathway boundaries. On myotubes immunoreactivity for NCAM remained low from stage 26 to 30 when it increased dramatically in both aneural and control limbs, indicating that its appearance is not triggered by nerve-dependent activity or trophic interactions. The increase was temporally associated with muscle cleavage and may encourage subsequent axon ramification as well as synaptogenesis. Staining remained high on muscle fibers during secondary myotube formation and only declined during the week before hatching when polyneuronal innervation is withdrawn and the mature synaptic pattern becomes stabilized. This loss of muscle NCAM occurred first on fast and then on slow muscle fibers. Together these results suggest that the timing of innervation may be controlled by the muscle, through NCAM expression, but that the subsequent suppression of muscle NCAM may occur as a result of nerve-mediated activity.
ESTHER : Tosney_1986_Dev.Biol_114_437
PubMedSearch : Tosney_1986_Dev.Biol_114_437
PubMedID: 3082698