Sato K

References (45)

Title : Transcriptome analysis revealed that PME-1 suppresses inflammatory signaling, activates PI3K\/Akt signaling, and promotes epithelial-mesenchymal transition - Ikeda_2023_Biochem.Biophys.Res.Commun_692_149148
Author(s) : Ikeda S , Sato K , Ohama T
Ref : Biochemical & Biophysical Research Communications , 692 :149148 , 2023
Abstract : Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that belongs to the type2A protein phosphatase family with PP4 and PP6. PP2A functions as a trimeric holoenzyme, and the composition of the trimer is regulated by the methyl-esterification (methylation) of PP2A. Demethylation of PP2A is catalyzed by protein phosphatase methyl-esterase-1 (PME-1). Despite the physiological and pathophysiological importance of PME-1, the impact of changes in PME-1 expression on the transcriptome has not been reported. This study provides transcriptome data to gain a comprehensive understanding of the effects of PME-1 knockout on intracellular signaling of mouse embryonic fibroblasts. Our data showed that PME-1 suppresses inflammatory signaling, activates PI3K/Akt signaling, and promotes epithelial-mesenchymal transition.
ESTHER : Ikeda_2023_Biochem.Biophys.Res.Commun_692_149148
PubMedSearch : Ikeda_2023_Biochem.Biophys.Res.Commun_692_149148
PubMedID: 38043157
Gene_locus related to this paper: human-PPME1

Title : Assessment of metabolic activation of felbamate in chimeric mice with humanized liver in combination with in vitro metabolic assays - Sato_2022_J.Toxicol.Sci_47_277
Author(s) : Sato K , Sanoh S , Ishida Y , Tateno C , Ohta S , Kotake Y
Ref : Journal of Toxicological Sciences , 47 :277 , 2022
Abstract : Felbamate (FBM) is an antiepileptic drug that has minimal toxicity in preclinical toxicological species but has a serious idiosyncratic drug toxicity (IDT) in humans. The formation of reactive metabolites is common among most drugs associated with IDT, and 2-phenylpropenal (2-PP) is believed to be the cause of IDT by FBM. It is important to consider the species difference in susceptibility to IDT between experimental animals and humans. In the present study, we used an in vitro and in vivo model system to reveal species difference in IDT of FBM. Human cytochrome P450 (CYP) and carboxylesterase (CES) expressing microsomes were used to clarify the isozymes involved in the metabolism of FBM. The remaining amount of FBM was significantly reduced in incubation with microsomes expressing human CYP2C8, 2C9, 2E1, and CES1c isozymes. Chimeric mice with humanized liver are expected to predict IDT in humans. Therefore, metabolite profiles in chimeric mice with humanized liver were investigated after administration of FBM. Metabolites after glutathione (GSH) conjugation of 2-phenylpropenal (2-PP), which is the reactive metabolite responsible for FBM-induced IDT, were detected in chimeric mice plasma and liver homogenate. Mass spectrometry imaging (MSI) visualizes distribution of FBM and endogenous GSH, and GSH levels in human hepatocyte were decreased after administration of FBM. In this study, we identified CYP and CES isozymes involved in the metabolism of FBM and confirmed reactive metabolite formation and subsequent decrease in GSH using humanized animal model. These results would provide useful information for the susceptibility to IDT between experimental animals and humans.
ESTHER : Sato_2022_J.Toxicol.Sci_47_277
PubMedSearch : Sato_2022_J.Toxicol.Sci_47_277
PubMedID: 35786679

Title : Atg15 in Saccharomyces cerevisiae consists of two functionally distinct domains - Hirata_2021_Mol.Biol.Cell__mbcE20070500
Author(s) : Hirata E , Shirai K , Kawaoka T , Sato K , Kodama F , Suzuki K
Ref : Mol Biology of the cell , :mbcE20070500 , 2021
Abstract : Autophagy is a cellular degradation system widely conserved among eukaryotes. During autophagy, cytoplasmic materials fated for degradation are compartmentalized in double membrane-bound organelles called autophagosomes. After fusing with the vacuole, their inner membrane-bound structures are released into the vacuolar lumen to become autophagic bodies and eventually degraded by vacuolar hydrolases. Atg15 is a lipase essential for disintegration of autophagic body membranes and has a transmembrane domain at the N-terminus and a lipase domain at the C-terminus. However, the roles of both domains in vivo are not well understood. In this study, we found that the N-terminal domain alone can travel to the vacuole via the multivesicular body pathway, and that targeting of the C-terminal lipase domain to the vacuole is required for degradation of autophagic bodies. Moreover, we found that the C-terminal domain could disintegrate autophagic bodies when it was transported to the vacuole via the Pho8 pathway instead of the multivesicular body pathway. Finally, we identified H435 as one of the residues composing the putative catalytic triad, and W466 as an important residue for degradation of autophagic bodies. This study may provide a clue to understanding how the C-terminal lipase domain recognizes autophagic bodies to degrade them. [Media: see text] [Media: see text].
ESTHER : Hirata_2021_Mol.Biol.Cell__mbcE20070500
PubMedSearch : Hirata_2021_Mol.Biol.Cell__mbcE20070500
PubMedID: 33625870
Gene_locus related to this paper: yeast-ATG15

Title : Involvement of PP2A methylation in the adipogenic differentiation of bone marrow-derived mesenchymal stem cell - Ikeda_2020_J.Biochem_168_643
Author(s) : Ikeda S , Tsuji S , Ohama T , Sato K
Ref : J Biochem , 168 :643 , 2020
Abstract : Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells with ability to self-replicate and differentiate into mesodermal derivatives, such as adipocytes and osteoblasts. BM-MSCs are a critical component of the tumour microenvironment. They support tumour progression by recruiting additional BM-MSCs and by differentiating into myofibroblasts (also called cancer-associated fibroblasts). Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that regulates a broad range of cellular signalling. PP2A forms a heterotrimer to dephosphorylate specific substrates. The reversible methylesterification (methylation) of Leu309 in the catalytic subunit of PP2A (PP2Ac) regulates biogenesis of the PP2A holoenzyme. It is unknown whether the methylation of PP2Ac plays a role in BM-MSC differentiation. Our experiments determined that protein levels of PP2A subunits and PP2A methyltransferase (LCMT-1) are significantly altered during differentiation. PP2Ac methylation levels in BM-MSCs decrease over time in response to an adipogenic differentiation stimulus. However, blockage of PP2A demethylation using the PP2A dimethyl-esterase inhibitors enhanced adipocyte differentiation. This suggests that PP2Ac demethylation is involved in adipocyte differentiation resistance. The results of our study provide a greater understanding of the regulation of BM-MSCs differentiation by PP2A holoenzyme.
ESTHER : Ikeda_2020_J.Biochem_168_643
PubMedSearch : Ikeda_2020_J.Biochem_168_643
PubMedID: 32663263
Gene_locus related to this paper: human-PPME1

Title : rCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer's disease after 18 months of treatment with the cholinesterase inhibitors donepezil or galantamine - Shirayama_2019_Brain.Imaging.Behav_13_75
Author(s) : Shirayama Y , Takahashi M , Oda Y , Yoshino K , Sato K , Okubo T , Iyo M
Ref : Brain Imaging Behav , 13 :75 , 2019
Abstract : Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naive late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.
ESTHER : Shirayama_2019_Brain.Imaging.Behav_13_75
PubMedSearch : Shirayama_2019_Brain.Imaging.Behav_13_75
PubMedID: 29247294

Title : Mechanism Underlying Organophosphate Paraoxon-Induced Kinetic Tremor - Iha_2019_Neurotox.Res_35_575
Author(s) : Iha HA , Kunisawa N , Shimizu S , Onishi M , Nomura Y , Matsubara N , Iwai C , Ogawa M , Hashimura M , Sato K , Kato M , Ohno Y
Ref : Neurotox Res , 35 :575 , 2019
Abstract : Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metabolite of parathion. Treating animals with paraoxon (0.15-0.6 mg/kg, i.p.) elicited kinetic tremor in a dose-dependent manner. Expressional analysis of Fos protein, a biomarker of neural excitation, revealed that a tremorgenic dose of paraoxon (0.6 mg/kg) significantly and region-specifically elevated Fos expression in the cerebral cortex (e.g., sensory cortex), hippocampal CA1, globus pallidus, medial habenula, and inferior olive (IO) among 48 brain regions examined. A moderate increase in Fos expression was also observed in the dorsolateral striatum while the change was not statistically significant. Paraoxon-induced tremor was inhibited by the nicotinic acetylcholine (nACh) receptor antagonist mecamylamine (MEC), but not affected by the muscarinic acetylcholine receptor antagonist trihexyphenidyl (THP). In addition, paraoxon-induced Fos expression in the IO was also antagonized by MEC, but not by THP, and lesioning of the IO markedly suppressed tremorgenic action of paraoxon. The present results suggest that OPs elicit kinetic tremor at least partly by activating IO neurons via nACh receptors.
ESTHER : Iha_2019_Neurotox.Res_35_575
PubMedSearch : Iha_2019_Neurotox.Res_35_575
PubMedID: 30729450

Title : The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer - Ishimine_2018_Dis.Markers_2018_5280736
Author(s) : Ishimine M , Lee HC , Nakaoka H , Orita H , Kobayashi T , Mizuguchi K , Endo M , Inoue I , Sato K , Yokomizo T
Ref : Dis Markers , 2018 :5280736 , 2018
Abstract : Irinotecan (CPT-11) is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37) showed lower CES2 mRNA levels (>/=1.5-fold lower) than the adjacent normal tissue, and only 30% (12 of 37) showed similar (<1.5-fold lower) or higher CES2 mRNA levels. However, TP53 gene sequencing revealed no relationship between CES2 downregulation and TP53 mutational status. Moreover, while colorectal cancer cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2, PRIMA-1(MET), a drug that restores the transcriptional activity of mutant p53, failed to upregulate CES2 expression in cells with TP53 missense mutations. These results, taken together, suggest that CES2 mRNA expression is decreased in human colorectal cancer independently of p53.
ESTHER : Ishimine_2018_Dis.Markers_2018_5280736
PubMedSearch : Ishimine_2018_Dis.Markers_2018_5280736
PubMedID: 29651325

Title : Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates - Hara_2018_Nat.Ecol.Evol_2_1761
Author(s) : Hara Y , Yamaguchi K , Onimaru K , Kadota M , Koyanagi M , Keeley SD , Tatsumi K , Tanaka K , Motone F , Kageyama Y , Nozu R , Adachi N , Nishimura O , Nakagawa R , Tanegashima C , Kiyatake I , Matsumoto R , Murakumo K , Nishida K , Terakita A , Kuratani S , Sato K , Hyodo S , Kuraku S
Ref : Nat Ecol Evol , 2 :1761 , 2018
Abstract : Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.
ESTHER : Hara_2018_Nat.Ecol.Evol_2_1761
PubMedSearch : Hara_2018_Nat.Ecol.Evol_2_1761
PubMedID: 30297745
Gene_locus related to this paper: scyto-a0a401nql2 , chipu-a0a401shd8 , chipu-a0a401rzt4 , scyto-a0a401q2n8 , scyto-a0a401nqq7 , chipu-a0a401s2p9 , scyto-a0a401q2m6 , chipu-a0a401rz56

Title : Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease - Hirano_2018_J.Alzheimers.Dis_62_1539
Author(s) : Hirano S , Shinotoh H , Shimada H , Ota T , Sato K , Tanaka N , Zhang MR , Higuchi M , Fukushi K , Irie T , Kuwabara S , Suhara T
Ref : J Alzheimers Dis , 62 :1539 , 2018
Abstract : BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. OBJECTIVE: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. METHODS: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. RESULTS: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. CONCLUSION: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.
ESTHER : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedSearch : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedID: 29562505

Title : Therapeutic effects of drug switching between acetylcholinesterase inhibitors in patients with Alzheimer's disease - Ohta_2017_Geriatr.Gerontol.Int_17_1843
Author(s) : Ohta Y , Darwish M , Hishikawa N , Yamashita T , Sato K , Takemoto M , Abe K
Ref : Geriatr Gerontol Int , 17 :1843 , 2017
Abstract : AIM: To evaluate the therapeutic effects of switching from one acetylcholinesterase inhibitor (ChEI), donepezil, galantamine or rivastigmine, to another in Alzheimer's disease patients. METHODS: We retrospectively enrolled 171 Alzheimer's disease patients, whose ChEI medication was changed. The patients were evaluated on three major aspects of dementia - cognitive, affective and activities of daily living (ADL) measures - at 6 months (M) before the drug switch, at the time of drug switch (baseline), and at 3 M and 6 M after the drug switch. RESULTS: The doses of the three ChEI were significantly lower at 6 M after the switch compared with the pre-switch doses. Improvements in apathy were found at 3 M when switching from donepezil to galantamine, but not to rivastigmine, but this switch had adverse effects on ADL. Improvements in cognitive scores at 3 M were also found when switching from galantamine to rivastigmine, but not to donepezil. However, both of these changes improved Abe's Behavioral and Psychological Symptoms of Dementia scores (ABS), except ADL. Switching from rivastigmine to donepezil worsened ABS at 6 M, but preserved cognitive and ADL scores. CONCLUSIONS: The present study suggests that despite a relatively lower dose of ChEI after the switch, switching from donepezil or rivastigmine preserved cognitive functions for at least 6 M. Switching from galantamine to rivastigmine improved Mini-Mental State Examination and ABS at 3 M, but did not improve ADL scores. Geriatr Gerontol Int 2017; 17: 1843-1848.
ESTHER : Ohta_2017_Geriatr.Gerontol.Int_17_1843
PubMedSearch : Ohta_2017_Geriatr.Gerontol.Int_17_1843
PubMedID: 28060449

Title : Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin\/Proteasome Degradation - Yabe_2015_PLoS.One_10_e0145226
Author(s) : Yabe R , Miura A , Usui T , Mudrak I , Ogris E , Ohama T , Sato K
Ref : PLoS ONE , 10 :e0145226 , 2015
Abstract : Protein phosphatase 2A (PP2A) is a conserved essential enzyme that is implicated as a tumor suppressor based on its central role in phosphorylation-dependent signaling pathways. Protein phosphatase methyl esterase (PME-1) catalyzes specifically the demethylation of the C-terminal Leu309 residue of PP2A catalytic subunit (PP2Ac). It has been shown that PME-1 affects the activity of PP2A by demethylating PP2Ac, but also by directly binding to the phosphatase active site, suggesting loss of PME-1 in cells would enhance PP2A activity. However, here we show that PME-1 knockout mouse embryonic fibroblasts (MEFs) exhibit lower PP2A activity than wild type MEFs. Loss of PME-1 enhanced poly-ubiquitination of PP2Ac and shortened the half-life of PP2Ac protein resulting in reduced PP2Ac levels. Chemical inhibition of PME-1 and rescue experiments with wild type and mutated PME-1 revealed methyl-esterase activity was necessary to maintain PP2Ac protein levels. Our data demonstrate that PME-1 methyl-esterase activity protects PP2Ac from ubiquitin/proteasome degradation.
ESTHER : Yabe_2015_PLoS.One_10_e0145226
PubMedSearch : Yabe_2015_PLoS.One_10_e0145226
PubMedID: 26678046
Gene_locus related to this paper: human-PPME1 , mouse-PPME1

Title : Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [(11) C]MP4A PET study - Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
Author(s) : Shimada H , Hirano S , Sinotoh H , Ota T , Tanaka N , Sato K , Yamada M , Fukushi K , Irie T , Zhang MR , Higuchi M , Kuwabara S , Suhara T
Ref : Int J Geriatr Psychiatry , 30 :1105 , 2015
Abstract : OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed.
RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000).
CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedSearch : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedID: 26280153

Title : Allosteric regulation of epoxide opening cascades by a pair of epoxide hydrolases in monensin biosynthesis - Minami_2014_ACS.Chem.Biol_9_562
Author(s) : Minami A , Ose T , Sato K , Oikawa A , Kuroki K , Maenaka K , Oguri H , Oikawa H
Ref : ACS Chemical Biology , 9 :562 , 2014
Abstract : Multistep catalysis of epoxide hydrolase/cyclase in the epoxide opening cascade is an intriguing issue in polyether biosynthesis. A pair of structurally homologous epoxide hydrolases was found in gene clusters of ionophore polyethers. In the epoxide opening reactions with MonBI and MonBII involved in monensin biosynthesis, we found that MonBII and catalytically inactive MonBI mutant catalyzed two-step reactions of bisepoxide substrate analogue to afford bicyclic product although MonBII alone catalyzed only the first cyclization. The X-ray crystal structure of MonBI dimers suggested the importance of the KSD motif in MonBI/MonBI interaction, which was further supported by gel filtration chromatography of wild-type MonBI and mutant MonBI. The involvement of the KSD motif in heterodimer formation was confirmed by in vitro assay. Direct evidence of MonBI/MonBII interaction was obtained by native mass spectrometry. Its dissociation constant was determined as 2.21 x 10(-5) M by surface plasmon resonance. Our results suggested the involvement of an allosteric regulation mechanism by MonBI/MonBII interaction in monensin skeletal construction.
ESTHER : Minami_2014_ACS.Chem.Biol_9_562
PubMedSearch : Minami_2014_ACS.Chem.Biol_9_562
PubMedID: 24320215

Title : A physical, genetic and functional sequence assembly of the barley genome - Mayer_2012_Nature_491_711
Author(s) : Mayer KF , Waugh R , Brown JW , Schulman A , Langridge P , Platzer M , Fincher GB , Muehlbauer GJ , Sato K , Close TJ , Wise RP , Stein N
Ref : Nature , 491 :711 , 2012
Abstract : Barley (Hordeum vulgare L.) is among the world's earliest domesticated and most important crop plants. It is diploid with a large haploid genome of 5.1 gigabases (Gb). Here we present an integrated and ordered physical, genetic and functional sequence resource that describes the barley gene-space in a structured whole-genome context. We developed a physical map of 4.98 Gb, with more than 3.90 Gb anchored to a high-resolution genetic map. Projecting a deep whole-genome shotgun assembly, complementary DNA and deep RNA sequence data onto this framework supports 79,379 transcript clusters, including 26,159 'high-confidence' genes with homology support from other plant genomes. Abundant alternative splicing, premature termination codons and novel transcriptionally active regions suggest that post-transcriptional processing forms an important regulatory layer. Survey sequences from diverse accessions reveal a landscape of extensive single-nucleotide variation. Our data provide a platform for both genome-assisted research and enabling contemporary crop improvement.
ESTHER : Mayer_2012_Nature_491_711
PubMedSearch : Mayer_2012_Nature_491_711
PubMedID: 23075845
Gene_locus related to this paper: horvd-f2e504 , horvv-f2dwm7 , horvv-f2cwp1 , horvv-m0utz9 , wheat-a0a3b6c2m6 , horvv-a0a287g9l8 , horvv-a0a287p3b9 , horvv-a0a287k7y5 , horvv-a0a287k830 , horvv-a0a287uvs9 , horvv-a0a287uvt3 , horvv-a0a287vga7 , horvv-a0a287w0t8 , horvv-a0a287rem5 , horvv-f2dfe3 , horvv-f2db09 , horvv-a0a8i7b938 , horvv-a0a287hj26 , horvv-f2e0h1

Title : Decreased resting energy expenditure in patients with Duchenne muscular dystrophy - Shimizu-Fujiwara_2012_Brain.Dev_34_206
Author(s) : Shimizu-Fujiwara M , Komaki H , Nakagawa E , Mori-Yoshimura M , Oya Y , Fujisaki T , Tokita Y , Kubota N , Shimazaki R , Sato K , Ishikawa T , Goto K , Mochizuki H , Takanoha S , Ogata K , Kawai M , Konagaya M , Miyazaki T , Tatara K , Sugai K , Sasaki M
Ref : Brain Dev , 34 :206 , 2012
Abstract : BACKGROUND: Skeletal muscle metabolism is a major determinant of resting energy expenditure (REE). Although the severe muscle loss that characterizes Duchenne muscular dystrophy (DMD) may alter REE, this has not been extensively investigated. METHODS: We studied REE in 77 patients with DMD ranging in age from 10 to 37 years using a portable indirect calorimeter, together with several clinical parameters (age, height, body weight (BW), body mass index (BMI), vital capacity (VC), creatine kinase, creatinine, albumin, cholinesterase, prealbumin), and assessed their influence on REE. In addition, in 12 patients maintaining a stable body weight, the ratio of energy intake to REE was calculated and defined as an alternative index for the physical activity level (aPAL). RESULTS: REE (kcal/day, mean+/-SD) in DMD patients was 1123 (10-11 years), 1186+/-188 (12-14 years), 1146+/-214 (15-17 years), 1006+/-136 (18-29 years) and 1023+/-97 (>/=30 years), each of these values being significantly lower than the corresponding control (p<0.0001). VC (p<0.001) was the parameter most strongly associated with REE, followed by BMI (p<0.01) and BW (p<0.05). The calculated aPAL values were 1.61 (10-11 years), 1.19 (12-14 years), 1.16 (15-17 years), and 1.57 (18-29 years). CONCLUSION: The REE in DMD patients was significantly lower than the normal value in every age group, and strongly associated with VC. Both the low REE and PAL values during the early teens, resulting in a low energy requirement, might be related to the obesity that frequently occurs in this age group. In contrast, the high PAL value in the late stage of the disease, possibly due to the presence of respiratory failure, may lead to a high energy requirement, and thus become one of the risk factors for development of malnutrition.
ESTHER : Shimizu-Fujiwara_2012_Brain.Dev_34_206
PubMedSearch : Shimizu-Fujiwara_2012_Brain.Dev_34_206
PubMedID: 21632191

Title : Nutritional status is strongly correlated with grip strength and depression in community-living elderly Japanese - Kaburagi_2011_Public.Health.Nutr_14_1893
Author(s) : Kaburagi T , Hirasawa R , Yoshino H , Odaka Y , Satomi M , Nakano M , Fujimoto E , Kabasawa K , Sato K
Ref : Public Health Nutr , 14 :1893 , 2011
Abstract : OBJECTIVES: To evaluate the utility of the Mini-Nutritional Assessment (MNA) in assessing nutritional, physical and psychosocial functions in community-living elderly individuals. DESIGN: A cross-sectional study of elderly individuals investigated in August 2007 and August-September 2008. Nutritional status was assessed using serum biomarkers, anthropometric measurements and the MNA. Physical function was assessed by measuring grip strength and both usual and maximum walking speeds. The Geriatric Depression Scale (GDS) was used to measure the individual's depressive state. SETTING: Elder-care facilities in Tokyo, Japan. SUBJECTS: Community-living elderly individuals aged >/=65 years (n 130). RESULTS: The MNA evaluation classified twenty-seven (20.8 %) individuals as being at risk for malnutrition (MNA score <=23.5); these at-risk individuals included a high proportion of the elderly aged >/=75 years. MNA scores correlated with nutritional biomarkers (total protein, albumin, cholinesterase, Hb) and anthropometric measurements (triceps skinfold, subscapular skinfold, mid-arm muscle area) and exhibited a strong correlation with grip strength and GDS score. Multivariate analysis revealed that grip strength, GDS score, marital status and maximum walking speed are strong predictors of MNA score. CONCLUSIONS: The MNA is considerably useful in providing a comprehensive assessment of nutritional status in elderly, community-living Japanese. However, larger-scale epidemiological studies are needed to determine the utility and the appropriate cut-off point of the MNA as a screen for risk of malnutrition.
ESTHER : Kaburagi_2011_Public.Health.Nutr_14_1893
PubMedSearch : Kaburagi_2011_Public.Health.Nutr_14_1893
PubMedID: 21426623

Title : Comprehensive sequence analysis of 24,783 barley full-length cDNAs derived from 12 clone libraries - Matsumoto_2011_Plant.Physiol_156_20
Author(s) : Matsumoto T , Tanaka T , Sakai H , Amano N , Kanamori H , Kurita K , Kikuta A , Kamiya K , Yamamoto M , Ikawa H , Fujii N , Hori K , Itoh T , Sato K
Ref : Plant Physiol , 156 :20 , 2011
Abstract : Full-length cDNA (FLcDNA) libraries consisting of 172,000 clones were constructed from a two-row malting barley cultivar (Hordeum vulgare 'Haruna Nijo') under normal and stressed conditions. After sequencing the clones from both ends and clustering the sequences, a total of 24,783 complete sequences were produced. By removing duplicates between these and publicly available sequences, 22,651 representative sequences were obtained: 17,773 were novel barley FLcDNAs, and 1,699 were barley specific. Highly conserved genes were found in the barley FLcDNA sequences for 721 of 881 rice (Oryza sativa) trait genes with 50% or greater identity. These FLcDNA resources from our Haruna Nijo cDNA libraries and the full-length sequences of representative clones will improve our understanding of the biological functions of genes in barley, which is the cereal crop with the fourth highest production in the world, and will provide a powerful tool for annotating the barley genome sequences that will become available in the near future.
ESTHER : Matsumoto_2011_Plant.Physiol_156_20
PubMedSearch : Matsumoto_2011_Plant.Physiol_156_20
PubMedID: 21415278
Gene_locus related to this paper: horvd-f2cta8 , horvd-f2cu28 , horvd-f2cu67 , horvd-f2cvb1 , horvd-f2d2e7 , horvd-f2d3b2 , horvd-f2d8w8 , horvd-f2dam1 , horvd-f2db20 , horvd-f2de38 , horvd-f2dey8 , horvd-f2djs2 , horvd-f2dlw1 , horvd-f2dnj9 , horvd-f2dnr0 , horvd-f2dq60 , horvd-f2dr75 , horvd-f2dvh4 , horvd-f2dwx9 , horvd-f2e2j6 , horvd-f2e3n3 , horvd-f2e504 , horvd-f2eb83 , horvd-f2ebk6 , horvd-f2ec44 , horvd-f2ecv3 , horvd-f2ee51 , horvd-f2eji1 , horvu-cp22 , orysa-q2qx94 , horvd-f2dey9 , horvd-f2djx2 , horvd-f2dln9 , horvd-f2dmr7 , horvd-f2dnv4 , horvd-f2drv9 , horvd-f2ds75 , horvd-f2dsx0 , horvd-f2e0a7 , horvd-f2e0u2 , horvd-f2e5v7 , horvd-f2d4p5 , horvd-m0vg59 , horvd-f2cqv0 , horvd-f2e1j3 , horvd-f2d241 , horvd-f2e8z5 , horvd-m0x298 , horvd-m0y280 , horvd-f2djb2 , horvd-f2dq90 , horvv-f2dwm7 , horvv-f2cwp1 , horvv-a0a287g9l8 , horvv-f2dfe3 , horvv-f2db09 , horvv-f2e0h1

Title : Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice - Shirakawa_2011_Diabetes_60_1246
Author(s) : Shirakawa J , Fujii H , Ohnuma K , Sato K , Ito Y , Kaji M , Sakamoto E , Koganei M , Sasaki H , Nagashima Y , Amo K , Aoki K , Morimoto C , Takeda E , Terauchi Y
Ref : Diabetes , 60 :1246 , 2011
Abstract : OBJECTIVE: Diet composition alters the metabolic states of adipocytes and hepatocytes in diabetes. The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation and fatty liver have been obscure. We investigated the extrapancreatic effects of DPP-4 inhibition on visceral fat and the liver. RESEARCH DESIGN AND METHODS: We investigated diet-induced metabolic changes in beta-cell-specific glucokinase haploinsufficient (Gck(+/-)) diabetic mice. We challenged animals with a diet containing a combination of sucrose and oleic acid (SO) or sucrose and linoleic acid (SL). Next, we assessed the effects of a DPP-4 inhibitor, des-fluoro-sitagliptin, on adipose tissue inflammation and hepatic steatosis. RESULTS: The epididymal fat weight and serum leptin level were significantly higher in Gck(+/-) mice fed SL than in mice fed SO, although no significant differences in body weight or adipocyte size were noted. Compared with SO, SL increased the numbers of CD11c(+) M1 macrophages and CD8(+) T-cells in visceral adipose tissue and the expression of E-selectin, P-selectin, and plasminogen activator inhibitor-1 (PAI-1). DPP-4 inhibition significantly prevented adipose tissue infiltration by CD8(+) T-cells and M1 macrophages and decreased the expression of PAI-1. The production of cytokines by activated T-cells was not affected by DPP-4 inhibition. Furthermore, DPP-4 inhibition prevented fatty liver in both wild-type and Gck(+/-) mice. DPP-4 inhibition also decreased the expressions of sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase-1, and fatty acid synthase, and increased the expression of peroxisome proliferator-activated receptor-alpha in the liver. CONCLUSIONS: Our findings indicated that DPP-4 inhibition has extrapancreatic protective effects against diet-induced adipose tissue inflammation and hepatic steatosis.
ESTHER : Shirakawa_2011_Diabetes_60_1246
PubMedSearch : Shirakawa_2011_Diabetes_60_1246
PubMedID: 21330637

Title : Tissue distribution of lipase genes related to triglyceride metabolism in laying hens (Gallus gallus) - Sato_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_155_62
Author(s) : Sato K , Seol HS , Kamada T
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 155 :62 , 2010
Abstract : The triglyceride lipase gene family, including lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), carboxyl ester lipase (CEL), endothelial lipase (EL), Lipase H, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), plays a critical role in lipid metabolism in mammals. In this study, we have identified and characterized the expression profile of these genes in the chicken, Gallus gallus. Chicken LPL and ATGL have been cloned, and HTGL, EL, Lipase H, and CEL sequences were found in the chicken genome database. The deduced amino acid sequences of HTGL, EL, Lipase H, and CEL were 66, 75, 63, and 65% identical with their respective human genes, suggesting conservation of important enzymatic functions. In contrast, a homologue of the HSL gene was not identified in the chicken genome. We performed RT-PCR using chicken liver, muscle, abdominal adipose tissue, or pancreas mRNA as the template, and all partial products were completely matched to the corresponding predicted sequences of triglyceride lipase gene members. Quantitation by qPCR of the transcript levels of these genes in 13 tissues indicates that the expression patterns diverge greatly between species. A particularly interesting pattern was observed in the distribution of EL and HTGL mRNA, which were highly expressed in kidney and ovary. This is the first report of HTGL, EL, Lipase H, and CEL in a pre-mammalian species and reveals novel details about specific features of the expression of these important molecules in lipid metabolism.
ESTHER : Sato_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_155_62
PubMedSearch : Sato_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_155_62
PubMedID: 19818411

Title : Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia - Hirano_2010_Brain_133_2058
Author(s) : Hirano S , Shinotoh H , Shimada H , Aotsuka A , Tanaka N , Ota T , Sato K , Ito H , Kuwabara S , Fukushi K , Irie T , Suhara T
Ref : Brain , 133 :2058 , 2010
Abstract : Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [11C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6+/-5.9 years), 12 with progressive supranuclear palsy (68.5+/-4.1 years), eight with frontotemporal dementia (59.8+/-6.9 years) and 16 healthy controls (61.2+/-8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k3 value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k3 images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k3 images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k3 values) in the paracentral region, frontal, parietal and occipital cortices (P<0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P<0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P<0.001), 9.4% in progressive supranuclear palsy (P<0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P<0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.
ESTHER : Hirano_2010_Brain_133_2058
PubMedSearch : Hirano_2010_Brain_133_2058
PubMedID: 20558417

Title : The effect of donepezil treatment on cardiovascular mortality - Sato_2010_Clin.Pharmacol.Ther_88_335
Author(s) : Sato K , Urbano R , Yu C , Yamasaki F , Sato T , Jordan J , Robertson D , Diedrich A
Ref : Clinical Pharmacology & Therapeutics , 88 :335 , 2010
Abstract : The acetylcholinesterase inhibitor donepezil hydrochloride improves cognitive function in patients with Alzheimer's disease and vascular dementia. Given acetylcholine's important actions on the heart, we undertook a retrospective cohort investigation to assess whether donepezil usage affects cardiovascular mortality. In patients treated with donepezil, hazard ratios for total and cardiovascular mortality were 0.68 (P = 0.045, 95% confidence interval 0.46-0.99) and 0.54 (P = 0.042, 95% confidence interval 0.30-0.98), respectively. The apparent survival benefit in donepezil-treated patients should not be overinterpreted. Prospective clinical trials are warranted.
ESTHER : Sato_2010_Clin.Pharmacol.Ther_88_335
PubMedSearch : Sato_2010_Clin.Pharmacol.Ther_88_335
PubMedID: 20664535

Title : Estimation of plasma IC50 of donepezil for cerebral acetylcholinesterase inhibition in patients with Alzheimer disease using positron emission tomography - Ota_2010_Clin.Neuropharmacol_33_74
Author(s) : Ota T , Shinotoh H , Fukushi K , Kikuchi T , Sato K , Tanaka N , Shimada H , Hirano S , Miyoshi M , Arai H , Suhara T , Irie T
Ref : Clinical Neuropharmacology , 33 :74 , 2010
Abstract : OBJECTIVES: Estimate the value of in vivo plasma IC50 of donepezil, the concentration of donepezil in plasma that inhibits brain acetylcholinesterase (AChE) activity by 50% at the steady-state conditions of donepezil between the plasma and the brain. METHODS: N-[C] methylpiperidin-4-yl acetate ([C]MP4A) positron emission tomography was performed in 16 patients with probable Alzheimer disease (AD) before and during the treatment of donepezil (5 mg/day) with a mean interval of 5.3 months. The plasma IC50 value of donepezil was estimated from plasma donepezil concentrations and cerebral cortical mean AChE inhibition rates measured by positron emission tomography, using one-parameter model. RESULTS: Donepezil reduced AChE activity uniformly in the cerebral cortex compared with the baseline in each AD patient, and the mean reduction rate in the cerebral cortex was 34.6%. The donepezil concentrations in the plasma ranged from 18.5 to 43.9 ng/mL with a mean of 28.9 +/- 7.3 ng/mL. The plasma IC50 value was estimated to be 53.6 +/- 4.0 ng/mL. CONCLUSIONS: Once the plasma IC50 of donepezil is determined, the brain AChE inhibition rate could be estimated from the plasma concentration of donepezil in each subject based on the plasma IC50. Now that the mean donepezil concentrations in the plasma, when the patients took 5 mg/day, remained 28.9 ng/mL, approximately half of the plasma IC50, higher dose of donepezil might provide further benefits for patients with AD. This technique can be also applied to measure the in vivo plasma IC50 of other cholinesterase inhibitors such as rivastigmine and galantamine.
ESTHER : Ota_2010_Clin.Neuropharmacol_33_74
PubMedSearch : Ota_2010_Clin.Neuropharmacol_33_74
PubMedID: 19935404

Title : Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET - Shimada_2009_Neurology_73_273
Author(s) : Shimada H , Hirano S , Shinotoh H , Aotsuka A , Sato K , Tanaka N , Ota T , Asahina M , Fukushi K , Kuwabara S , Hattori T , Suhara T , Irie T
Ref : Neurology , 73 :273 , 2009
Abstract : OBJECTIVE: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). METHODS: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. RESULTS: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. CONCLUSIONS: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.
ESTHER : Shimada_2009_Neurology_73_273
PubMedSearch : Shimada_2009_Neurology_73_273
PubMedID: 19474411

Title : PET study of brain acetylcholinesterase in cerebellar degenerative disorders - Hirano_2008_Mov.Disord_23_1154
Author(s) : Hirano S , Shinotoh H , Arai K , Aotsuka A , Yasuno F , Tanaka N , Ota T , Sato K , Fukushi K , Tanada S , Hattori T , Irie T
Ref : Movement Disordersord , 23 :1154 , 2008
Abstract : To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.
ESTHER : Hirano_2008_Mov.Disord_23_1154
PubMedSearch : Hirano_2008_Mov.Disord_23_1154
PubMedID: 18412283

Title : Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells - Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
Author(s) : Damirin A , Tomura H , Komachi M , Liu JP , Mogi C , Tobo M , Wang JQ , Kimura T , Kuwabara A , Yamazaki Y , Ohta H , Im DS , Sato K , Okajima F
Ref : American Journal of Physiology Heart Circ Physiol , 292 :H2513 , 2007
Abstract : The migration of vascular smooth muscle cells (SMCs) is a hallmark of the pathogenesis of atherosclerosis and restenosis after angioplasty. Plasma low-density lipoprotein (LDL), but not high-density lipoprotein (HDL), induced the migration of human coronary artery SMCs (CASMCs). Among bioactive lipids postulated to be present in LDL, lysophosphatidic acid (LPA) appreciably mimicked the LDL action. In fact, the LDL-induced migration was markedly inhibited by pertussis toxin, an LPA receptor antagonist Ki-16425, and a small interfering RNA (siRNA) targeted for LPA(1) receptors. Moreover, LDL contains a higher amount of LPA than HDL does. HDL markedly inhibited LPA- and platelet-derived growth factor (PDGF)-induced migration, and sphingosine 1-phosphate (S1P), the content of which is about fourfold higher in HDL than in LDL, mimicked the HDL action. The inhibitory actions of HDL and S1P were suppressed by S1P(2) receptor-specific siRNA. On the other hand, the degradation of the LPA component of LDL by monoglyceride lipase or the antagonism of LPA receptors by Ki-16425 allowed LDL to inhibit the PDGF-induced migration. The inhibitory effect of LDL was again suppressed by S1P(2) receptor-specific siRNA. In conclusion, LPA/LPA(1) receptors and S1P/S1P(2) receptors mediate the stimulatory and inhibitory migration response to LDL and HDL, respectively. The balance of not only the content of LPA and S1P in lipoproteins but also the signaling activity between LPA(1) and S1P(2) receptors in the cells may be critical in determining whether the lipoprotein is a positive or negative regulator of CASMC migration.
ESTHER : Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
PubMedSearch : Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
PubMedID: 17237247

Title : Gene expression profiles of drug-metabolizing enzymes and transporters with an overexpression of hepatocyte growth factor - Kakizaki_2007_Liver.Int_27_109
Author(s) : Kakizaki S , Yamazaki Y , Kosone T , Horiguchi N , Sohara N , Sato K , Takagi H , Yoshinari K , Mori M
Ref : Liver Int , 27 :109 , 2007
Abstract : BACKGROUND: It is important to elucidate the precise mechanism of drug metabolism during hepatic regeneration. Although cytochromes P450 (CYPs) are well known to be down-regulated in growth-stimulated cells, the overall gene expression profile of drug metabolizing enzymes are still not fully understood during hepatic regeneration. In this study, we investigated the gene expression profiles of such enzymes with an overexpression of hepatocyte growth factor (HGF). METHODS: Gene expression profiles were obtained using the Affymetrix MOE430A GeneChip oligonucleotide microarray by comparing HGF transgenic mice and wild-type mice. RESULTS: HGF produced a general decrease in mice with the expression of CYP isoforms such as Cyp1a2, Cyp2b10, Cyp2c, Cyp2d9, Cyp3a11, Cyp4a10, and Cyp7a1. Some isoforms of alcohol dehydrogenase, aldehyde dehydrogenase, and carboxylesterase also decreased. In the phase II enzymes, some isoforms of glutathione S-transferase and UDP-glucuronosyl transferase showed a reduced expression, although the sulfotransferase did not. In phase III transporters, some organic anion transporter and organic cation transporters were down-regulated. Among the nuclear receptors that are known to regulate the drug-metabolizing enzymes, small heterodimer partner and constitutive androstane receptor were down-regulated with an HGF overexpression. The protein level and enzymatic activity of Cyp2c decreased with an HGF overexpression. We furthermore investigated the inducibility of Cyp2b10 with xenobiotic inducers. Although the basal expression of Cyp2b10 was repressed, the inducibility was not abolished with the HGF overexpression. CONCLUSIONS: HGF down-regulated not only CYPs but also some drug-metabolizing enzymes, transporters, and nuclear receptors. We thus have to take in our mind the low basal expression of drug metabolizing enzymes, when treating patients with a regenerative liver state.
ESTHER : Kakizaki_2007_Liver.Int_27_109
PubMedSearch : Kakizaki_2007_Liver.Int_27_109
PubMedID: 17241389

Title : Estimation of plasma IC50 of donepezil hydrochloride for brain acetylcholinesterase inhibition in monkey using N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) and PET - Shiraishi_2005_Neuropsychopharmacology_30_2154
Author(s) : Shiraishi T , Kikuchi T , Fukushi K , Shinotoh H , Nagatsuka S , Tanaka N , Ota T , Sato K , Hirano S , Tanada S , Iyo M , Irie T
Ref : Neuropsychopharmacology , 30 :2154 , 2005
Abstract : Donepezil hydrochloride is a potent and selective inhibitor for brain acetylcholinesterase (AChE) and is currently used worldwide for the treatment of Alzheimer's disease. Until now, there is no in vivo study on the relation between the plasma concentration and the brain AChE inhibition. The purpose of this study was to estimate in vivo plasma IC(50) of donepezil in living monkeys by measuring plasma donepezil concentration (LC/MS/MS) and brain AChE activity with positron emission tomography (PET) and N-[(11)C]methylpiperidin-4-yl acetate, which is an acetylcholine analog recently developed by us for quantifying in vivo brain AChE activity. PET scans with donepezil at two doses, 100 microg/kg (donepezil-1; N=5) or 250 microg/kg (donepezil-2; N=5), were performed using the same monkeys at 4-week intervals. Before each PET scan, baseline PET scans (N=10 in total) were performed without donepezil. The plasma donepezil concentrations 14 min after intravenous injection were proportional to the doses, 17.2+/-2.9 ng/ml (donepezil-1) and 44.0+/-5.0 ng/ml (donepezil-2), and the mean AChE inhibitions in four neocortical regions as evaluated by PET were also dose-dependent, 27% (donepezil-1) and 53% (donepezil-2). In IC(50) estimation, measured plasma donepezil concentrations were corrected for the change during PET scan. The IC(50) values (estimate+/-SE) were 42+/-9.0 (ng/ml; donepezil-1), 34+/-3.2 (donepezil-2), and 37+/-4.1 (combined data). The present method may be useful for in vivo evaluation of other AChE inhibitors and novel drugs.
ESTHER : Shiraishi_2005_Neuropsychopharmacology_30_2154
PubMedSearch : Shiraishi_2005_Neuropsychopharmacology_30_2154
PubMedID: 15920507

Title : Regulation of p38 phosphorylation and topoisomerase IIalpha expression in the B-cell lymphoma line Jiyoye by CD26\/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin - Yamochi_2005_Cancer.Res_65_1973
Author(s) : Yamochi T , Aytac U , Sato T , Sato K , Ohnuma K , McKee KS , Morimoto C , Dang NH
Ref : Cancer Research , 65 :1973 , 2005
Abstract : CD26 is a Mr 110,000 surface-bound glycoprotein with diverse functional properties, including having a key role in normal T-cell physiology and the development of certain cancers. In this article, we show that surface expression of CD26, especially its intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity, results in enhanced topoisomerase IIalpha level in the B-cell line Jiyoye and subsequent in vitro sensitivity to doxorubicin-induced apoptosis. In addition, we show that expression of CD26/DPPIV is associated with increased phosphorylation of p38 and its upstream regulators mitogen-activated protein kinase kinase 3/6 and apoptosis signal-regulating kinase 1 and that p38 signaling pathway plays a role in the regulation of topoisomerase IIalpha expression. Besides demonstrating that CD26 effect on topoisomerase IIalpha and doxorubicin sensitivity is applicable to cell lines of both B-cell and T-cell lineages, the potential clinical implication of our work lies with the fact that we now show for the first time that our in vitro results can be extended to a severe combined immunodeficient mouse model. Our findings that CD26 expression can be an in vivo marker of tumor sensitivity to doxorubicin treatment may lead to future treatment strategies targeting CD26/DPPIV for selected human cancers in the clinical setting. Our article thus characterizes the biochemical linkage among CD26, p38, and topoisomerase IIalpha while providing evidence that CD26-associated topoisomerase IIalpha expression results in greater in vitro and in vivo tumor sensitivity to the antineoplastic agent doxorubicin.
ESTHER : Yamochi_2005_Cancer.Res_65_1973
PubMedSearch : Yamochi_2005_Cancer.Res_65_1973
PubMedID: 15753397

Title : Evaluation of simplified kinetic analyses for measurement of brain acetylcholinesterase activity using N-[11C]Methylpiperidin-4-yl propionate and positron emission tomography - Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
Author(s) : Sato K , Fukushi K , Shinotoh H , Nagatsuka S , Tanaka N , Aotsuka A , Ota T , Shiraishi T , Tanada S , Iyo M , Irie T
Ref : Journal of Cerebral Blood Flow & Metabolism , 24 :600 , 2004
Abstract : The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.
ESTHER : Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
PubMedSearch : Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
PubMedID: 15181367

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 : Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: Functional imaging of the conscious monkey brain using animal PET in combination with microdialysis - Tsukada_2004_Synapse_52_1
Author(s) : Tsukada H , Nishiyama S , Fukumoto D , Ohba H , Sato K , Kakiuchi T
Ref : Synapse , 52 :1 , 2004
Abstract : This study demonstrated the effects of acute acetylcholinesterase (AChE) inhibition by donepezil (Aricept) on the cerebral cholinergic neuronal system in the brains of young (5.2 +/- 1.1 years old) and aged (20.3 +/- 2.6 years old) monkeys (Macaca mulatta) in the conscious state. Donepezil at doses of 50 and 250 microg/kg suppressed AChE activity, analyzed by metabolic rate (k(3)) of N-[(11)C]methyl-4-piperidyl acetate ([(11)C]MP4A), in all cortical regions in a dose-dependent manner in both age groups. However, the suppression degree was more marked in young than in aged monkeys. AChE inhibition by donepezil resulted in a dose-dependent increase in acetylcholine levels in the prefrontal cortex of young animals as measured by microdialysis. Binding of (+)N-[(11)C]propyl-3-piperidyl benzilate ([(11)C](+)3-PPB) to cortical muscarinic receptors was reduced by donepezil, probably in a competitive inhibition manner. Aged monkeys showed less reduction of [(11)C](+)3-PPB binding than young animals. As evaluated by an oculomotor delayed response task, aged monkeys showed impaired working memory performance compared to young monkeys, and the impaired performance was partly improved by the administration of donepezil, due to the facilitation of the cholinergic neuronal system by AChE inhibition. These results demonstrate that the PET imaging technique with specific labeled compounds in combination with microdialysis and a behavioral cognition task could be a useful method to clarify the mechanism of drugs in the living brains of experimental animals.
ESTHER : Tsukada_2004_Synapse_52_1
PubMedSearch : Tsukada_2004_Synapse_52_1
PubMedID: 14755627

Title : Association of lipoprotein lipase gene polymorphism with risk of prostate cancer in a Japanese population - Narita_2004_Int.J.Cancer_112_872
Author(s) : Narita S , Tsuchiya N , Wang L , Matsuura S , Ohyama C , Satoh S , Sato K , Ogawa O , Habuchi T , Kato T
Ref : International Journal of Cancer , 112 :872 , 2004
Abstract : A high fat intake has been associated with prostate cancer risk, and gene polymorphisms of lipoprotein lipase (LPL) play an important role in plasma lipoprotein metabolism. We herein analyzed the association of LPL gene polymorphisms with the risk of prostate cancer in a Japanese population. Three single nucleotide polymorphisms (SNPs) of LPL designated as Ser447stop, HindIII and PvuII were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 273 prostate cancer patients, 205 benign prostatic hyperplasia (BPH) patients and 230 male controls. The men with the CG + GG genotypes of the Ser447stop polymorphism had an increased risk of prostate cancer compared to those with the CC genotype [age-adjusted odds ratio (aOR) = 1.625; 95% CI = 1.068-2.471; p = 0.023]. Furthermore, the increased risk associated with the CG + GG genotypes was more strongly observed in patients with high-grade cancers (aOR = 2.843; 95% CI = 1.252-6.458; p = 0.039) or metastatic diseases (aOR = 2.300; 95% CI = 1.042-5.074; p = 0.013), whereas the risk was not significant in those with low- to intermediate-grade cancers or nonmetastatic diseases. In the HindIII and PvuII polymorphisms, there was no significant difference between the prostate cancer patients and the controls, and no significant results as for tumor grade and stage. None of the 3 polymorphisms showed any association with the risk of BPH. Our results suggest that the LPL Ser447stop polymorphism is a common genetic modifier for the development of prostate cancer, particularly that of high-grade and/or high-stage, in a Japanese population.
ESTHER : Narita_2004_Int.J.Cancer_112_872
PubMedSearch : Narita_2004_Int.J.Cancer_112_872
PubMedID: 15386377

Title : A simple method for the detection of abnormal brain regions in Alzheimer's disease patients using [11C]MP4A: comparison with [123I]IMP SPECT - Ota_2004_Ann.Nucl.Med_18_187
Author(s) : Ota T , Shinotoh H , Fukushi K , Nagatsuka S , Namba H , Iyo M , Aotsuka A , Tanaka N , Sato K , Shiraishi T , Tanada S , Arai H , Irie T
Ref : Ann Nucl Med , 18 :187 , 2004
Abstract : We have developed a radiolabeled lipophilic acetylcholine analogue, N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) to measure brain acetylcholinesterase (AChE) activity by positron emission tomography (PET) in vivo. Aiming to develop a new SPECT tracer similar to MP4A, we first proposed a simple method for diagnosing Alzheimer's disease (AD) using [11C]MP4A PET. We performed [11C]MP4A PET and N-isopropyl [123I]iodoamphetamine ([123I]IMP) SPECT in 13 patients with AD and in 17 normal controls (NC). We calculated the ratio of radioactivity of the cortical region of interest (ROI) to that of the cerebellum measured with [11C]MP4A PET (MP4A ratio) and the ratio of regional cerebral blood flow (rCBF) to that of the cerebellum measured with [123I]IMP SPECT (IMP ratio). Eleven cortical ROIs were placed in the frontal, sensorimotor, temporal, parietal, and occipital cortices in both hemispheres and in the posterior cingulate cortex, and z-score was calculated in each ROI in patients with AD compared with NC. When the z-score was 2 or more in a ROI, it was defined as a positive ROI. When a patient had 3 or more positive ROIs, the patient was diagnosed as having AD. The reduction in the MP4A ratio was greater than that in the IMP ratio in all cortical ROIs except for in the right parietal cortex and cingulate cortex in patients with AD. MP4A ratio method showed 92% sensitivity and the IMP ratio method 69% sensitivity for the diagnosis of AD. These results encourage us to develop a new SPECT tracer similar to MP4A for the diagnosis of AD.
ESTHER : Ota_2004_Ann.Nucl.Med_18_187
PubMedSearch : Ota_2004_Ann.Nucl.Med_18_187
PubMedID: 15233279

Title : Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred - Sato_2004_J.Hum.Genet_49_29
Author(s) : Sato K , Emi M , Ezura Y , Fujita Y , Takada D , Ishigami T , Umemura S , Xin Y , Wu LL , Larrinaga-Shum S , Stephenson SH , Hunt SC , Hopkins PN
Ref : J Hum Genet , 49 :29 , 2004
Abstract : Plasma lipid and lipoprotein in general reflect the complex influences of multiple genetic loci, for instance, even familial hypercholesterolemia (FH), a representative example of monogenic hyperlipidemia, often presents with phenotypic heterogeneity. In the course of investigating familial coronary artery disease in Utah, we studied 160 members of an eight-generation extended family of FH in which 69 members were affected with type IIa hyperlipoproteinemia (HLPIIa; high plasma cholesterol) and ten with type IIb hyperlipoproteinemia (HLPIIb; high plasma cholesterol as well as plasma triglyceride). Soluble epoxide hydrolase ( EPHX2, sEH) plays a role in disposition of epoxides in plasma lipoprotein particles. Intrafamilial correlation analysis of the modifier effect of Glu287Arg substitution in the EPHX2 gene was carried out among 79 LDLR mutation carriers and 81 noncarriers. In the carriers, plasma cholesterol levels were elevated among carriers of the 287Arg allele (mean +/- SD=358 +/- 72 mg/dl) in comparison with 287Glu homozygotes (mean +/- SD=302 +/- 72 mg/dl) (p=0.0087). Similarly, in the LDLR mutation carriers, the plasma triglyceride levels were elevated among carriers of the 287Arg allele (mean +/- SD=260 +/- 100 mg/dl) in comparison with 287Glu homozygotes (mean +/- SD=169 +/- 83 mg/dl) (p=0.020). No such gene-interactive effect was observed among noncarriers of the LDLR mutation. Half of the patients who presented with HLPIIb had inherited a defective LDLR allele as well as an EPHX2-287Arg allele, whereas the majority who presented with HLPIIa had a defective LDLR allele but not an EPHX2-287Arg allele. These results indicate a significant modification of the phenotype of FH with defective LDLR allele by EPHX2-287Arg variation in our studied kindred.
ESTHER : Sato_2004_J.Hum.Genet_49_29
PubMedSearch : Sato_2004_J.Hum.Genet_49_29
PubMedID: 14673705
Gene_locus related to this paper: human-EPHX2

Title : Long-term effects of donepezil on P300 auditory event-related potentials in patients with Alzheimer's disease - Katada_2003_J.Geriatr.Psychiatry.Neurol_16_39
Author(s) : Katada E , Sato K , Sawaki A , Dohi Y , Ueda R , Ojika K
Ref : J Geriatr Psychiatry Neurol , 16 :39 , 2003
Abstract : The P300, one of the cognitive event-related potentials (ERPs) of the cerebral cortex, reflects the functioning of the neurochemical system involved in cognitive processes. We investigated clinical significance of the components of auditory P300 ERPs, in comparison with neuropsychologic tests including the Mini-Mental State Examination and the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog), for evaluating of the effect of donepezil (DPZ) (5 mg daily for 6 months), an acetylcholinesterase inhibitor, in patients with Alzheimer's disease (AD). Reduction of P300 latency associated with a parallel improvement of ADAS-J cog scores was observed after administration of 5 mg/day of DPZ in patients with AD. P300 latency gives very useful information on the progression of AD, especially in the longitudinal follow-up of patients with AD during treatment with DPZ acting on cholinergic pathways.
ESTHER : Katada_2003_J.Geriatr.Psychiatry.Neurol_16_39
PubMedSearch : Katada_2003_J.Geriatr.Psychiatry.Neurol_16_39
PubMedID: 12641372

Title : Collection, mapping, and annotation of over 28,000 cDNA clones from japonica rice - Kikuchi_2003_Science_301_376
Author(s) : Kikuchi S , Satoh K , Nagata T , Kawagashira N , Doi K , Kishimoto N , Yazaki J , Ishikawa M , Yamada H , Ooka H , Hotta I , Kojima K , Namiki T , Ohneda E , Yahagi W , Suzuki K , Li CJ , Ohtsuki K , Shishiki T , Otomo Y , Murakami K , Iida Y , Sugano S , Fujimura T , Suzuki Y , Tsunoda Y , Kurosaki T , Kodama T , Masuda H , Kobayashi M , Xie Q , Lu M , Narikawa R , Sugiyama A , Mizuno K , Yokomizo S , Niikura J , Ikeda R , Ishibiki J , Kawamata M , Yoshimura A , Miura J , Kusumegi T , Oka M , Ryu R , Ueda M , Matsubara K , Kawai J , Carninci P , Adachi J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Hayatsu N , Imotani K , Ishii Y , Itoh M , Kagawa I , Kondo S , Konno H , Miyazaki A , Osato N , Ota Y , Saito R , Sasaki D , Sato K , Shibata K , Shinagawa A , Shiraki T , Yoshino M , Hayashizaki Y , Yasunishi A
Ref : Science , 301 :376 , 2003
Abstract : We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.
ESTHER : Kikuchi_2003_Science_301_376
PubMedSearch : Kikuchi_2003_Science_301_376
PubMedID: 12869764
Gene_locus related to this paper: orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9FYP7 , orysa-Q5JLP6 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-cbp3 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q7F1B1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q6ZDG5 , orysa-Q658B2 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-q2qnj4 , orysa-q2qyi1 , orysa-Q4VWY7 , orysa-q5smv5 , orysa-q5z901 , orysa-Q5ZBI5 , orysa-q6atz0 , orysa-q6i5q3 , orysj-q6yse8 , orysa-q6z8b1 , orysa-q6z995 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr63 , orysa-q7xsq2 , orysa-q7xts6 , orysa-Q8LQS5 , orysa-Q8W3C6 , orysa-q53m20 , orysa-q67iz3 , orysa-q67j02 , orysa-q67j05 , orysa-q67j09 , orysa-q67j10 , orysa-q67tv0 , orysa-q67uz1 , orysa-q69xr2 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-b8a7e7 , orysi-b8bfe5 , orysj-cgep , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6

Title : Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection - Maeno_2003_J.Gastroenterol.Hepatol_18_1358
Author(s) : Maeno T , Okumura A , Ishikawa T , Kato K , Sakakibara F , Sato K , Ayada M , Hotta N , Tagaya T , Fukuzawa Y , Kakumu S
Ref : J Gastroenterol Hepatol , 18 :1358 , 2003
Abstract : BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance.
METHODS: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated.
RESULTS: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.
ESTHER : Maeno_2003_J.Gastroenterol.Hepatol_18_1358
PubMedSearch : Maeno_2003_J.Gastroenterol.Hepatol_18_1358
PubMedID: 14675263

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp

Title : Functional annotation of a full-length mouse cDNA collection - Kawai_2001_Nature_409_685
Author(s) : Kawai J , Shinagawa A , Shibata K , Yoshino M , Itoh M , Ishii Y , Arakawa T , Hara A , Fukunishi Y , Konno H , Adachi J , Fukuda S , Aizawa K , Izawa M , Nishi K , Kiyosawa H , Kondo S , Yamanaka I , Saito T , Okazaki Y , Gojobori T , Bono H , Kasukawa T , Saito R , Kadota K , Matsuda H , Ashburner M , Batalov S , Casavant T , Fleischmann W , Gaasterland T , Gissi C , King B , Kochiwa H , Kuehl P , Lewis S , Matsuo Y , Nikaido I , Pesole G , Quackenbush J , Schriml LM , Staubli F , Suzuki R , Tomita M , Wagner L , Washio T , Sakai K , Okido T , Furuno M , Aono H , Baldarelli R , Barsh G , Blake J , Boffelli D , Bojunga N , Carninci P , de Bonaldo MF , Brownstein MJ , Bult C , Fletcher C , Fujita M , Gariboldi M , Gustincich S , Hill D , Hofmann M , Hume DA , Kamiya M , Lee NH , Lyons P , Marchionni L , Mashima J , Mazzarelli J , Mombaerts P , Nordone P , Ring B , Ringwald M , Rodriguez I , Sakamoto N , Sasaki H , Sato K , Schonbach C , Seya T , Shibata Y , Storch KF , Suzuki H , Toyo-oka K , Wang KH , Weitz C , Whittaker C , Wilming L , Wynshaw-Boris A , Yoshida K , Hasegawa Y , Kawaji H , Kohtsuki S , Hayashizaki Y
Ref : Nature , 409 :685 , 2001
Abstract : The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
ESTHER : Kawai_2001_Nature_409_685
PubMedSearch : Kawai_2001_Nature_409_685
PubMedID: 11217851
Gene_locus related to this paper: mouse-1lipg , mouse-1plip , mouse-1plrp , mouse-ABH15 , mouse-abhd5 , mouse-ABHD6 , mouse-Abhd8 , mouse-aryla , mouse-bphl , mouse-cauxin , mouse-Ces1g , mouse-CPMac , mouse-dpp8 , mouse-EPHX1 , mouse-ES10 , mouse-hslip , mouse-hyes , mouse-ABHD2 , mouse-lcat , mouse-lipli , mouse-LIPN , mouse-lypla1 , mouse-lypla2 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-Ppgb , mouse-PPME1 , mouse-ppt , mouse-q3uuq7 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-RISC , mouse-SERHL , mouse-SPG21 , mouse-Tex30

Title : Evaluation of PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate and (+)N-[(11)C]propyl-3-piperidyl benzilate for muscarinic cholinergic receptors: a PET study with microdialysis in comparison with (+)N-[(11)C]methyl-3-piperidyl benzilate in the conscious monkey brain - Nishiyama_2001_Synapse_40_159
Author(s) : Nishiyama S , Tsukada H , Sato K , Kakiuchi T , Ohba H , Harada N , Takahashi K
Ref : Synapse , 40 :159 , 2001
Abstract : We developed PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate ([(11)C](+)3-EPB) and (+)N-[(11)C]propyl-3-piperidyl benzilate ([(11)C](+)3-PPB) for cerebral muscarinic cholinergic receptors. The distribution and kinetics of the novel ligands were evaluated for comparison with the previously reported ligand (+)N-[(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB) in the monkey brain (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). At 60-91 min postinjection, regional distribution patterns of these three ligands were almost identical, and were consistent with the muscarinic receptor density in the brain as previously reported in vitro. However, the time-activity curves of [(11)C](+)3-EPB and [(11)C](+)3-PPB showed earlier peak times of radioactivity and a faster clearance rate than [(11)C](+)3-MPB in cortical regions rich in the receptors. Kinetic analysis using the three-compartment model with time-activity curves of radioactivity in metabolite-corrected arterial plasma as input functions revealed that labeling with longer [(11)C]alkyl chain length induced lower binding potential (BP = k(3)/k(4)), consistent with the rank order of affinity of these ligands obtained by an in vitro assay using rat brain slices and [(3)H]QNB. The cholinesterase inhibitor Aricept administered at doses of 50 and 250 microg/kg increased acetylcholine level in extracellular fluid of the frontal cortex and the binding of [(11)C](+)3-PPB with the lowest affinity to the receptors was displaced by the endogenous acetylcholine induced by cholinesterase inhibition, while [(11)C](+)3-MPB with the highest affinity was not significantly affected. Taken together, these observations indicate that the increase in [(11)C]alkyl chain length could alter the kinetic properties of conventional receptor ligands for PET by reducing the affinity to receptors, which might make it possible to assess the interaction between endogenous neurotransmitters and ligand-receptor binding in vivo as measured by PET.
ESTHER : Nishiyama_2001_Synapse_40_159
PubMedSearch : Nishiyama_2001_Synapse_40_159
PubMedID: 11304753

Title : Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain - Tsukada_2000_Brain.Res_857_158
Author(s) : Tsukada H , Sato K , Kakiuchi T , Nishiyama S
Ref : Brain Research , 857 :158 , 2000
Abstract : The effects of three cholinesterase inhibitors (physostigmine, E2020, and Tacrine), all of which are to be cognitive enhancers, on the functional regional cerebral blood flow (rCBF) response were studied in young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys under awake conditions using high-resolution positron emission tomography (PET). Under control condition, vibrotactile stimulation elicited increases in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in rCBF response was significantly lower in aged (115.8%) than that in young monkeys (139.9%). Regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, measured using [18F]-2-fluoro-2-deoxy-Dphysostigmine) were consistent with the data obtained by microdialysis. In contrast, the cognitive enhancers did not alter rCBF response to stimulation in young monkeys. The present results demonstrated that the functional change in rCBF response to the stimulation was induced during the aging process by impairment of the coupling mechanism between the neuronal activation and rCBF response. Furthermore, the observation that cognitive enhancers partly restored the functional rCBF response suggested that the coupling mechanism might be regulated via cholinergic neuronal transmission.
ESTHER : Tsukada_2000_Brain.Res_857_158
PubMedSearch : Tsukada_2000_Brain.Res_857_158
PubMedID: 10700563

Title : Cloning of mouse prolidase cDNA: predominant expression of prolidase mRNA in kidney - Ishii_1996_Biochim.Biophys.Acta_31_15
Author(s) : Ishii T , Tsujino S , Matsunobu S , Endo F , Sato K , Sakuragawa N
Ref : Biochimica & Biophysica Acta , 31 :15 , 1996
Abstract : We cloned mouse prolidase cDNA from a mouse liver cDNA library. Homology to human prolidase is 83.2% at the nucleotide level and 87.2% at the amino acid level. Northern blot analysis showed that while prolidase mRNA was transcribed in brain, heart, liver, and muscle, it was predominantly transcribed in kidney.
ESTHER : Ishii_1996_Biochim.Biophys.Acta_31_15
PubMedSearch : Ishii_1996_Biochim.Biophys.Acta_31_15
PubMedID: 8765744

Title : Acetylcholine determination of cerebrospinal fluid in aneurysmal subarachnoid hemorrhage - Kawamata_1994_Surg.Neurol_41_399
Author(s) : Kawamata T , Takeshita M , Ujiie H , Sato K , Izawa M , Kagawa M , Takakura K
Ref : Surg Neurol , 41 :399 , 1994
Abstract : Acetylcholine (ACh) concentrations were determined serially in cerebrospinal fluid (CSF) obtained from 23 patients with aneurysmal subarachnoid hemorrhage (SAH) by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). The values of CSF ACh were significantly low in the initial stage of SAH, and increased subsequently but they did not return to control values within 3 weeks. In addition, serial measurements of CSF butyrylcholinesterase (BChE) activity in 12 SAH patients showed that the activity was elevated significantly in the initial stage of SAH and returned to control levels within a week. This discrepancy in the recovery period between the ACh levels and the BChE activity in CSF indicated that significantly lower CSF ACh levels after SAH could not be attributed to plasma BChE contamination of CSF These results suggested central cholinergic dysfunction after SAH especially in the initial stage
ESTHER : Kawamata_1994_Surg.Neurol_41_399
PubMedSearch : Kawamata_1994_Surg.Neurol_41_399
PubMedID: 8009415

Title : Inhibition by lithium of cyclic GMP formation without inhibition of nitric oxide generation in the mouse neuroblastoma cell (N1E-115) - Shintani_1994_Neuropsychopharmacology_11_119
Author(s) : Shintani F , Kanba S , Nakaki T , Nakamura R , Sato K , Yagi G , Richelson E , Kato R , Asai M
Ref : Neuropsychopharmacology , 11 :119 , 1994
Abstract : We investigated the effects of lithium ion (Li+) on muscarinic receptor-mediated nitric oxide (NO) generation, and guanylate cyclase (GCase) activation using the mouse neuroblastoma clone, N1E-115. The levels of released NO were determined by measuring the levels of nitrite/nitrate in the incubation medium, and the activity of GCase was measured with an assay for cellular cyclic [3H] GMP levels. We determined that Li+ had no effects on muscarinic receptor-activated elevation of nitrite/nitrate levels, which were significantly inhibited by 100 microM L-NG-monomethylarginine, although it has been reported that Li+ inhibits muscarinic receptor-activated cyclic GMP formation in the cells. In addition, Li+ inhibited the cyclic GMP formation induced by an NO donor, sodium nitroprusside (SNP), in both intact cells and a crude cellular homogenate; thus, the inhibition by Li+ of muscarinic receptor-mediated cyclic GMP synthesis appeared to be at the level of GCase, but not NO synthase.
ESTHER : Shintani_1994_Neuropsychopharmacology_11_119
PubMedSearch : Shintani_1994_Neuropsychopharmacology_11_119
PubMedID: 7840863

Title : Changes in carboxylesterase isoenzymes of rat liver microsomes during hepatocarcinogenesis - Maki_1991_Jpn.J.Cancer.Res_82_800
Author(s) : Maki T , Hosokawa M , Satoh T , Sato K
Ref : Jpn J Cancer Research , 82 :800 , 1991
Abstract : Among the three major carboxylesterase isoenzymes, RH1, RL1 and RL2, present in microsomes from normal rat liver, RL2 shows hydrolyzing activity towards 12-O-tetradecanoylphorbol-13-acetate and 1-oleoy1-2-acetyl-rac-glycerol, both activators of protein kinase C. Since protein kinase C has been suggested to be involved in carcinogenesis and cell proliferation, alterations in hepatic microsomal carboxylesterase isoenzymes including RL2 were studied during hepatocarcinogenesis induced by the Solt-Farber model. Alteration of RL2 was determined by measuring acetanilide-hydrolyzing activity, by quantifying the protein amount using the single radial immunodiffusion method, and by activity staining following electrophoresis of liver microsomes. The isoenzyme composition of hepatic microsomal carboxylesterase was changed after partial hepatectomy, and marked decreases in RL2 activity and protein content were observed at 4 weeks, at the time of preneoplastic foci induction. Partial hepatectomy alone also resulted in decreased RL2 activity. These findings suggest that RL2 may be involved in regulation of protein kinase C activity by metabolizing its activators at an early stage of hepatocarcinogenesis in rats.
ESTHER : Maki_1991_Jpn.J.Cancer.Res_82_800
PubMedSearch : Maki_1991_Jpn.J.Cancer.Res_82_800
PubMedID: 1908847