Sato T

References (39)

Title : Donepezil, an anti-Alzheimer's disease drug, promotes differentiation and regeneration in injured skeletal muscle through the elevation of the expression of myogenic regulatory factors - Todaka_2021_Eur.J.Pharmacol__174528
Author(s) : Todaka H , Arikawa M , Noguchi T , Ichikawa A , Sato T
Ref : European Journal of Pharmacology , :174528 , 2021
Abstract : We previously demonstrated that donepezil, an anti-Alzheimer's disease drug, improved skeletal muscle atrophy by enhancing the angiogenesis of endothelial cells and activating the proliferation of satellite cells in a mouse model of peripheral arterial disease. However, the effect of donepezil on muscle differentiation during regeneration remains unclear. Therefore, we measured the expressions of myogenic regulatory factors and late muscle differentiation markers in donepezil-treated C2C12 myoblast cells before and after the induction of cell differentiation. The results indicate that the expressions of myogenin, troponin T (TnT) and myosin heavy chain (MyHC) were significantly increased and myotube formation was accelerated in donepezil-treated cells under the differentiation condition. However, the promotive effect of donepezil on muscle differentiation could not be reproduced by the addition of acetylcholine (ACh) and was not disrupted after treatment with ACh receptor blockers. Moreover, other kinds of acetylcholinesterase inhibitors failed to promote muscle differentiation in C2C12 cells. These results indicate that the specific characteristics of donepezil in the promotion of muscle differentiation are independent of its acetylcholinesterase-inhibitory action. We further found that donepezil induced an incremental shift of the cross-sectional area of myofibers and elevated the expressions of myogenin, TnT and MyHC in a mouse model of cardiotoxin injury. These results suggest that donepezil promotes the differentiation of muscle regeneration upon injury via the elevation of the expressions of myogenic regulatory factors and late muscle differentiation markers. Our findings suggest that donepezil can be a useful therapeutic agent for injured skeletal muscle treatment.
ESTHER : Todaka_2021_Eur.J.Pharmacol__174528
PubMedSearch : Todaka_2021_Eur.J.Pharmacol__174528
PubMedID: 34582845

Title : Shear Wave Dispersion Predicts Liver Fibrosis and Adverse Outcomes in Patients with Heart Failure - Ohara_2020_J.Clin.Med_9_
Author(s) : Ohara H , Yoshihisa A , Ishibashi S , Matsuda M , Yamadera Y , Sugawara Y , Ichijo Y , Hotsuki Y , Watanabe K , Anzai F , Sato Y , Kimishima Y , Yokokawa T , Misaka T , Sato T , Oikawa M , Kobayashi A , Takeishi Y
Ref : J Clin Med , 9 : , 2020
Abstract : BACKGROUND: It has been recently reported that liver stiffness assessed by transient elastography reflects right atrial pressure (RAP) and is associated with worse outcomes in patients with heart failure (HF). However, the relationship between shear wave dispersion (SWD, a novel indicator of liver viscosity) determined by abdominal ultrasonography and RAP, and the prognostic impact of SWD on HF patients have not been fully examined. We aimed to clarify the associations of SWD with parameters of liver function test (LFT) and right heart catheterization (RHC), as well as with cardiac events such as cardiac death and worsening HF, in patients with HF. METHODS: We performed abdominal ultrasonography, LFT and RHC in HF patients (n = 195), and followed up for cardiac events. We examined associations between SWD and parameters of LFT and RHC. RESULTS: There were significant correlations between SWD and circulating levels of direct bilirubin (R = 0.222, p = 0.002), alkaline phosphatase (R = 0.219, p = 0.002), cholinesterase (R = -0.184, p = 0.011), and 7S domain of collagen type IV (R = 0.177, p = 0.014), but not with RAP (R = 0.054, p = 0.567) or cardiac index (R = -0.015, p = 0.872). In the Kaplan-Meier analysis, cardiac event rate was significantly higher in the high SWD group (SWD >= 10.0 (m/s)/kHz, n = 103) than in the low SWD group (SWD < 10.0 (m/s)/kHz, n = 92; log-rank, p = 0.010). In the Cox proportional hazard analysis, high SWD was associated with high cardiac event rates (hazard ratio, 2.841; 95% confidence interval, 1.234-6.541, p = 0.014). In addition, there were no interactions between SWD and all subgroups, according to the subgroup analysis. CONCLUSIONS: SWD assessed by abdominal ultrasonography reflects liver fibrosis rather than liver congestion, and is associated with adverse prognosis in HF patients.
ESTHER : Ohara_2020_J.Clin.Med_9_
PubMedSearch : Ohara_2020_J.Clin.Med_9_
PubMedID: 33291248

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

Title : DPP8 is a novel therapeutic target for multiple myeloma - Sato_2019_Sci.Rep_9_18094
Author(s) : Sato T , Tatekoshi A , Takada K , Iyama S , Kamihara Y , Jawaid P , Rehman MU , Noguchi K , Kondo T , Kajikawa S , Arita K , Wada A , Murakami J , Arai M , Yasuda I , Dang NH , Hatano R , Iwao N , Ohnuma K , Morimoto C
Ref : Sci Rep , 9 :18094 , 2019
Abstract : Dipeptidyl peptidases (DPPs) are proteolytic enzymes that are ideal therapeutic targets in human diseases. Indeed, DPP4 inhibitors are widely used in clinical practice as anti-diabetic agents. In this paper, we show that DPP4 inhibitors also induced cell death in multiple human myeloma cells. Among five DPP4 inhibitors, only two of them, vildagliptin and saxagliptin, exhibited apparent cytotoxic effects on myeloma cell lines, without any difference in suppression of DPP4 activity. As these two DPP4 inhibitors are known to have off-target effects against DPP8/9, we employed the specific DPP8/9 inhibitor 1G244. 1G244 demonstrated anti-myeloma effects on several cell lines and CD138+ cells from patients as well as in murine xenograft model. Through siRNA silencing approach, we further confirmed that DPP8 but not DPP9 is a key molecule in inducing cell death induced by DPP8/9 inhibition. In fact, the expression of DPP8 in CD38+ cells from myeloma patients was higher than that of healthy volunteers. DPP8/9 inhibition induced apoptosis, as evidenced by activated form of PARP, caspases-3 and was suppressed by the pan-caspase inhibitor Z-VAD-FMK. Taken together, these results indicate that DPP8 is a novel therapeutic target for myeloma treatment.
ESTHER : Sato_2019_Sci.Rep_9_18094
PubMedSearch : Sato_2019_Sci.Rep_9_18094
PubMedID: 31792328
Gene_locus related to this paper: human-DPP8

Title : Conversion of carlactone to carlactonoic acid is a conserved function of MAX1 homologs in strigolactone biosynthesis - Yoneyama_2018_New.Phytol_218_1522
Author(s) : Yoneyama K , Mori N , Sato T , Yoda A , Xie X , Okamoto M , Iwanaga M , Ohnishi T , Nishiwaki H , Asami T , Yokota T , Akiyama K , Nomura T
Ref : New Phytol , 218 :1522 , 2018
Abstract : Strigolactones (SLs) are a class of plant hormones which regulate shoot branching and function as host recognition signals for symbionts and parasites in the rhizosphere. However, steps in SL biosynthesis after carlactone (CL) formation remain elusive. This study elucidated the common and diverse functions of MAX1 homologs which catalyze CL oxidation. We have reported previously that ArabidopsisMAX1 converts CL to carlactonoic acid (CLA), whereas a rice MAX1 homolog has been shown to catalyze the conversion of CL to 4-deoxyorobanchol (4DO). To determine which reaction is conserved in the plant kingdom, we investigated the enzymatic function of MAX1 homologs in Arabidopsis, rice, maize, tomato, poplar and Selaginella moellendorffii. The conversion of CL to CLA was found to be a common reaction catalyzed by MAX1 homologs, and MAX1s can be classified into three types: A1-type, converting CL to CLA; A2-type, converting CL to 4DO via CLA; and A3-type, converting CL to CLA and 4DO to orobanchol. CLA was detected in root exudates from poplar and Selaginella, but not ubiquitously in other plants examined in this study, suggesting its role as a species-specific signal in the rhizosphere. This study provides new insights into the roles of MAX1 in endogenous and rhizosphere signaling.
ESTHER : Yoneyama_2018_New.Phytol_218_1522
PubMedSearch : Yoneyama_2018_New.Phytol_218_1522
PubMedID: 29479714

Title : Donepezil, an acetylcholinesterase inhibitor, attenuates LPS-induced inflammatory response in murine macrophage cell line RAW 264.7 through inhibition of nuclear factor kappa B translocation - Arikawa_2016_Eur.J.Pharmacol_789_17
Author(s) : Arikawa M , Kakinuma Y , Noguchi T , Todaka H , Sato T
Ref : European Journal of Pharmacology , 789 :17 , 2016
Abstract : We have previously demonstrated that the pharmacotherapy with donepezil, an acetylcholinesterase inhibitor, suppresses cardiac remodeling in a mouse model of ischemic heart failure after myocardial infarction (MI). However, the precise mechanisms of the cardioprotective effect of donepezil have not been completely delineated. Because post-ischemic inflammation is a pathological key event in the cardiac remodeling process following MI, we investigated the hypothesis that donepezil acts as an inhibitor of inflammatory mediators. RAW 264.7 murine macrophage cells were pretreated with donepezil (100microM) prior to a pro-inflammatory stimulation by administration of lipopolysaccharide (LPS, 10ng/ml). Donepezil significantly reduced intra- and extracellular levels of various kinds of inflammatory mediators such as TNF-alpha, IL-1beta, IL-2, IL-6 and IL-18 after the LPS stimulation, and attenuated LPS-induced nuclear translocation of nuclear factor-kappa B (NF-kappaB). These results indicate that donepezil possesses an anti-inflammatory property. However, the inhibitory effect of donepezil on the macrophage inflammatory responses was never reproduced by ACh, nor was disrupted by ACh receptor blockers. Moreover, other kinds of acetylcholinesterase inhibitors failed to inhibit the inflammatory responses in LPS-stimulated macrophage cells. These results suggest that a cholinergic anti-inflammatory pathway would not be involved in the anti-inflammatory effect of donepezil and that the specific characteristics of donepezil in suppressing the LPS-induced cytokine release and the NF-kappaB activation would be independent of its acetylcholinesterase inhibition. The present study showed that donepezil exerts an anti-inflammatory effect independently of acetylcholinesterase inhibitory action, thereby donepezil may contribute to cardioprotection during cardiac remodeling process in an ischemic heart failure after MI.
ESTHER : Arikawa_2016_Eur.J.Pharmacol_789_17
PubMedSearch : Arikawa_2016_Eur.J.Pharmacol_789_17
PubMedID: 27373848

Title : Biodegradable Plastic-degrading Activity of Various Species of Paraphoma - Koitabashi_2016_J.Oleo.Sci_65_621
Author(s) : Koitabashi M , Sameshima-Yamashita Y , Koike H , Sato T , Moriwaki J , Morita T , Watanabe T , Yoshida S , Kitamoto H
Ref : J Oleo Sci , 65 :621 , 2016
Abstract : The fungal strain B47-9, isolated from barley, was previously selected as an effective degrader of various biodegradable plastic (BP) films such as poly(butylene succinate-co-adipate) (PBSA) and poly(butylene succinate) (PBS). The strain has not been identified based on mycological methods because it does not form fruiting bodies, which are the key to morphological identification. Here, we performed molecular phylogenetic analyses of the nuclear ribosomal RNA gene regions and their internal transcribed spacer region of B47-9 and related fungi. The results suggest that B47-9 is closely related to the genus Paraphoma. Investigation of the abilities of six strains belonging to the genus Paraphoma to degrade BPs indicated that all strains could degrade PBSA and PBS films to varying degrees. Based on our approach, we conclude that strain B47-9 is a species belonging to the genus Paraphoma.
ESTHER : Koitabashi_2016_J.Oleo.Sci_65_621
PubMedSearch : Koitabashi_2016_J.Oleo.Sci_65_621
PubMedID: 27321123

Title : Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase - Sato_2015_Heliyon_1_e00013
Author(s) : Sato T , Enoki Y , Sakamoto Y , Yokota K , Okubo M , Matsumoto M , Hayashi N , Usui M , Kokabu S , Mimura T , Nakazato Y , Araki N , Fukuda T , Okazaki Y , Suda T , Takeda S , Yoda T
Ref : Heliyon , 1 :e00013 , 2015
Abstract : OBJECTIVE: Donepezil, an inhibitor of acetylcholinesterase (AChE) targeting the brain, is a common medication for Alzheimer's disease. Interestingly, a recent clinical study found that administration of this agent is associated with lower risk of hip fracture independently of falling, suggesting its direct effect on bone tissues as well. AChE has been reported to be involved in osteoblast function, but the role of AChE on osteoclastogenesis still remains unclear. We analyzed the effect of AChE and donepezil on osteoclastogenesis in vivo and in vitro.
METHODS: Cell-based assays were conducted using osteoclasts generated in cultures of murine bone marrow macrophages (BMMs) with receptor activator of nuclear factor-kappa B ligand (RANKL). The effect of donepezil was also determined in vivo using a mouse model of RANKL-induced bone loss.
RESULTS: Recombinant AChE in BMMs cultured with RANKL further promoted RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation. RANKL also upregulated AChE expression in BMMs. RNA interference-mediated knockdown of AChE significantly inhibited RANKL-induced osteoclast differentiation and suppressed gene expression specific for osteoclasts. AChE upregulated expression of RANK, the receptor of RANKL, in BMMs. Donepezil decreased cathepsin K expression in BMMs and the resorptive function of osteoclasts on dentine slices. Donepezil decreased RANK expression in BMMs, resulting in the inhibition of osteoclast differentiation with downregulation of c-Fos and upregulation of Id2. Moreover, administration of donepezil prevented RANKL-induced bone loss in vivo, which was associated with the inhibition of bone resorption by osteoclasts.
CONCLUSIONS: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.
ESTHER : Sato_2015_Heliyon_1_e00013
PubMedSearch : Sato_2015_Heliyon_1_e00013
PubMedID: 27441211

Title : Serum cholinesterase is an important prognostic factor in chronic heart failure - Sato_2015_Heart.Vessels_30_204
Author(s) : Sato T , Yamauchi H , Suzuki S , Yoshihisa A , Yamaki T , Sugimoto K , Kunii H , Nakazato K , Suzuki H , Saitoh S , Takeishi Y
Ref : Heart Vessels , 30 :204 , 2015
Abstract : We determine the importance of indicators of nutrition including lymphocyte, total protein, albumin, cholinesterase and body mass index, and compare the prognostic significance in chronic heart failure (CHF). We examined consecutive 465 CHF patients (376 males, age 62 +/- 14 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination including indicators of nutrition at the same time in our hospital. The patients were followed up [median period 766 days (interquartile range 500-1060)] to register cardiac deaths and rehospitalization due to worsening heart failure. There were 180 cardiac events during the follow-up periods. Patients with cardiac events had lower cholinesterase level than those without events (P < 0.001). On the receiver operating characteristic analysis, the best cut-off value for cholinesterase was 240 U/l (area under the curve 0.720). In the Kaplan-Meier analysis, patients with cholinesterase <240 U/l had significantly higher cardiac event rates than those with cholinesterase >240 U/l. Multivariable Cox proportional hazards model demonstrated that NYHA class III [hazard ratio (HR): 1.688, 95 % confidence interval (CI) 1.062-2.684, P = 0.027], eGFR (HR: 0.983, 95 % CI 0.971-0.995, P = 0.006), sodium concentration (HR: 0.947, 95 % CI 0.897-0.999, P < 0.046), log BNP (HR: 1.880, 95 % CI 1.509-2.341, P < 0.001), cholinesterase (HR: 0.996, 95 % CI 0.993-0.998, P = 0.002) and exertional periodic breathing (HR: 1.619, 95 % CI 1.098-2.388, P = 0.015) were independent factors to predict adverse clinical outcomes. Serum cholinesterase level was an important prognostic factor in CHF.
ESTHER : Sato_2015_Heart.Vessels_30_204
PubMedSearch : Sato_2015_Heart.Vessels_30_204
PubMedID: 24463844

Title : Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy - Koie_2014_ScientificWorldJournal_2014_948305
Author(s) : Koie T , Ohyama C , Mikami J , Iwamura H , Fujita N , Sato T , Kojima Y , Fukushi K , Yamamoto H , Imai A , Hatakeyama S , Yoneyama T , Hashimoto Y , Kitayama M , Hirota K
Ref : ScientificWorldJournal , 2014 :948305 , 2014
Abstract : The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168-470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of >/=100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.
ESTHER : Koie_2014_ScientificWorldJournal_2014_948305
PubMedSearch : Koie_2014_ScientificWorldJournal_2014_948305
PubMedID: 24741368

Title : Antimuscle atrophy effect of nicotine targets muscle satellite cells partly through an alpha7 nicotinic receptor in a murine hindlimb ischemia model - Kakinuma_2014_Transl.Res_164_32
Author(s) : Kakinuma Y , Noguchi T , Okazaki K , Oikawa S , Iketani M , Kurabayashi M , Furihata M , Sato T
Ref : Transl Res , 164 :32 , 2014
Abstract : We have recently identified that donepezil, an anti-Alzheimer drug, accelerates angiogenesis in a murine hindlimb ischemia (HLI) model. However, the precise mechanisms are yet to be fully elucidated, particularly whether the effects are derived from endothelial cells alone or from other nonvascular cells. Further investigation of the HLI model revealed that nicotine accelerated angiogenesis by activation of vascular endothelial cell growth factor (VEGF) synthesis through nicotinic receptors in myogenic cells, that is, satellite cells, in vivo and upregulated the expression of angiogenic factors, for example, VEGF and fibroblast growth factor 2, in vitro. As a result, nicotine prevented skeletal muscle from ischemia-induced muscle atrophy and upregulated myosin heavy chain expression in vitro. The in vivo anti-atrophy effect of nicotine on muscle was also observed in galantamine, another anti-Alzheimer drug, playing as an allosteric potentiating ligand. Such effects of nicotine were attenuated in alpha7 nicotinic receptor knockout mice. In contrast, PNU282987, an alpha7 nicotinic receptor agonist, comparably salvaged skeletal muscle, which was affected by HLI. These results suggest that cholinergic signals also target myogenic cells and have inhibiting roles in muscle loss by ischemia-induced muscle atrophy.
ESTHER : Kakinuma_2014_Transl.Res_164_32
PubMedSearch : Kakinuma_2014_Transl.Res_164_32
PubMedID: 24811002

Title : Complete Genome Sequence of Pseudomonas sp. Strain TKP, Isolated from a gamma-Hexachlorocyclohexane-Degrading Mixed Culture - Ohtsubo_2014_Genome.Announc_2_e01241
Author(s) : Ohtsubo Y , Kishida K , Sato T , Tabata M , Kawasumi T , Ogura Y , Hayashi T , Tsuda M , Nagata Y
Ref : Genome Announc , 2 : , 2014
Abstract : Pseudomonas sp. strain TKP does not degrade gamma-hexachlorocyclohexane (gamma-HCH), but it persistently coexists with the gamma-HCH-degrading Sphingobium sp. strain TKS in a mixed culture enriched by gamma-HCH. Here, we report the complete genome sequence of strain TKP, which consists of one circular chromosome with a size of 7 Mb.
ESTHER : Ohtsubo_2014_Genome.Announc_2_e01241
PubMedSearch : Ohtsubo_2014_Genome.Announc_2_e01241
PubMedID: 24482516
Gene_locus related to this paper: psefl-e2xn15 , psefs-c3k632 , psefs-laaa , psefs-c3k813 , psefl-e2xkc8 , 9psed-v9qxq1 , 9psed-v9qr47

Title : Donepezil can improve ischemic muscle atrophy by activating angiomyogenic properties of satellite cells - Noguchi_2014_Circ.J_78_2317
Author(s) : Noguchi T , Kakinuma Y , Arikawa M , Okazaki K , Hoshino E , Iiyama T , Kubo T , Kitaoka H , Doi Y , Sato T
Ref : Circ J , 78 :2317 , 2014
Abstract : BACKGROUND: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD.Methods and Results:In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1alpha, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1beta, and fibroblast growth factor 2 protein.
CONCLUSIONS: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD. (Circ J 2014; 78: 2317-2324).
ESTHER : Noguchi_2014_Circ.J_78_2317
PubMedSearch : Noguchi_2014_Circ.J_78_2317
PubMedID: 25070503

Title : Complete Genome Sequence of Pseudomonas aeruginosa MTB-1, Isolated from a Microbial Community Enriched by the Technical Formulation of Hexachlorocyclohexane - Ohtsubo_2014_Genome.Announc_2_e01130
Author(s) : Ohtsubo Y , Sato T , Kishida K , Tabata M , Ogura Y , Hayashi T , Tsuda M , Nagata Y
Ref : Genome Announc , 2 : , 2014
Abstract : Pseudomonas aeruginosa MTB-1 does not degrade gamma-hexachlorocyclohexane (gamma-HCH), but this bacterium persistently coexists with a gamma-HCH-degrading strain, Sphingomonas sp. MM-1, in a microbial community enriched by the technical formulation of HCH. Here we report the complete MTB-1 genome sequence, with a 6.6-Mb circular chromosome.
ESTHER : Ohtsubo_2014_Genome.Announc_2_e01130
PubMedSearch : Ohtsubo_2014_Genome.Announc_2_e01130
PubMedID: 24459257
Gene_locus related to this paper: pseae-PA3695 , pseae-PA5080 , pseae-q9i252

Title : Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides from beta-Lactoglobulin Secreted by Lactococcus lactis - Shigemori_2014_Biomed.Res.Int_2014_393598
Author(s) : Shigemori S , Oshiro K , Wang P , Yamamoto Y , Wang Y , Sato T , Uyeno Y , Shimosato T
Ref : Biomed Res Int , 2014 :393598 , 2014
Abstract : Previous studies showed that hydrolysates of beta-lactoglobulin (BLG) prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV) activity in vitro. In this study, we developed a BLG-secreting Lactococcus lactis strain as a delivery vehicle and in situ expression system. Interestingly, trypsin-digested recombinant BLG from L. lactis inhibited DPP-IV activity, suggesting that BLG-secreting L. lactis may be useful in the treatment of type 2 diabetes mellitus.
ESTHER : Shigemori_2014_Biomed.Res.Int_2014_393598
PubMedSearch : Shigemori_2014_Biomed.Res.Int_2014_393598
PubMedID: 25157356

Title : Heart-specific overexpression of choline acetyltransferase gene protects murine heart against ischemia through hypoxia-inducible factor-1alpha-related defense mechanisms - Kakinuma_2013_J.Am.Heart.Assoc_2_e004887
Author(s) : Kakinuma Y , Tsuda M , Okazaki K , Akiyama T , Arikawa M , Noguchi T , Sato T
Ref : J Am Heart Assoc , 2 :e004887 , 2013
Abstract : BACKGROUND: Murine and human ventricular cardiomyocytes rich in acetylcholine (Ach) receptors are poorly innervated by the vagus, compared with whole ventricular innervation by the adrenergic nerve. However, vagal nerve stimulation produces a favorable outcome even in the murine heart, despite relatively low ventricular cholinergic nerve density. Such a mismatch and missing link suggest the existence of a nonneuronal cholinergic system in ventricular myocardium. METHODS AND
RESULTS: To examine the role of the nonneuronal cardiac cholinergic system, we generated choline acetyltransferase (ChAT)-expressing cells and heart-specific ChAT transgenic (ChAT-tg) mice. Compared with cardiomyocytes of wild-type (WT) mice, those of the ChAT-tg mice had high levels of ACh and hypoxia-inducible factor (HIF)-1alpha protein and augmented glucose uptake. These phenotypes were also reproduced by ChAT-overexpressing cells, which utilized oxygen less. Before myocardial infarction (MI), the WT and ChAT-tg mice showed similar hemodynamics; after MI, however, the ChAT-tg mice had better survival than did the WT mice. In the ChAT-tg hearts, accelerated angiogenesis at the ischemic area, and accentuated glucose utilization prevented post-MI remodeling. The ChAT-tg heart was more resistant to ischemia-reperfusion injury than was the WT heart.
CONCLUSIONS: These results suggest that the activated cardiac ACh-HIF-1alpha cascade improves survival after MI. We conclude that de novo synthesis of ACh in cardiomyocytes is a pivotal mechanism for self-defense against ischemia.
ESTHER : Kakinuma_2013_J.Am.Heart.Assoc_2_e004887
PubMedSearch : Kakinuma_2013_J.Am.Heart.Assoc_2_e004887
PubMedID: 23525439

Title : Potential clinical factors affecting hepatobiliary enhancement at Gd-EOB-DTPA-enhanced MR imaging - Higaki_2012_Magn.Reson.Imaging_30_689
Author(s) : Higaki A , Tamada T , Sone T , Kanki A , Sato T , Tanimoto D , Higashi H , Ito K
Ref : Magn Reson Imaging , 30 :689 , 2012
Abstract : OBJECTIVE: The objective was to clarify the clinical factors that might affect the degree of hepatic parenchymal enhancement at gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: A total of 84 patients with (n=63) and without chronic liver disease (n=21) underwent Gd-EOB-DTPA-enhanced MR imaging. Contrast-enhanced MR images of hepatobiliary phase (HP) were obtained at 20 min after Gd-EOB-DTPA administration. The relative enhancement (RE) of liver parenchyma at 20 min HP was calculated from region of interest measurements at each patient. Then, these results were correlated with various clinical parameters using Pearson correlation coefficient or Spearman rank correlation coefficient. Furthermore, the predictor of the degree of hepatic parenchymal enhancement was determined using multiple regression analysis. RESULTS: The presence or absence of chronic liver disease (P=.002), ascites (P=.005) and splenomegaly (P=.027), and the values of prothrombin activity (P=.008), total bilirubin (T-Bil) (P=.001), albumin (P=.001), aspartate aminotransferase (AST) (P=.002) and cholinesterase (P=.007) were significantly correlated with the RE of liver parenchyma at 20 min HP. Among these parameters, increases of T-Bil (P=.011 to .028) and AST (P=.018 to .049) were predictors of decreased hepatic parenchymal enhancement. CONCLUSIONS: Hepatic parenchymal enhancement of Gd-EOB-DTPA was affected by various clinical parameters. Impaired hepatobiliary enhancement may be predicted by routine biochemical tests, such as T-Bil and AST.
ESTHER : Higaki_2012_Magn.Reson.Imaging_30_689
PubMedSearch : Higaki_2012_Magn.Reson.Imaging_30_689
PubMedID: 22459437

Title : Influences of Donepezil on Cardiovascular System-Possible Therapeutic Benefits for Heart Failure-DOnepezil Cardiac TEst Registry (DOCTER) Study - Kubo_2012_J.Cardiovasc.Pharmacol_60_310
Author(s) : Kubo T , Sato T , Noguchi T , Kitaoka H , Yamasaki F , Kamimura N , Shimodera S , Iiyama T , Kumagai N , Kakinuma Y , Diedrich A , Jordan J , Robertson D , Doi YL
Ref : J Cardiovasc Pharmacol , 60 :310 , 2012
Abstract : ABSTRACT To study prospectively influences of donepezil an acetylcholinesterase inhibitor against Alzheimer disease on cardiovascular system we evaluated cardiovascular changes occurring during new initialized treatment with donepezil in 49 dementia patients over 6 months No patient suffered from cardiovascular events In clinical changes between baseline and the first evaluation after donepezil treatment heart rate and plasma brain natriuretic peptide BNP levels as a marker for heart failure did not change BNP 59.62 62.71 pg/mL at baseline to 53.18 42.34 pg/mL at first evaluation P 0.262 We further examined plasma BNP levels in 2 groups into which the patients were divided at baseline according to the cut-off plasma BNP level of 60 pg/mL In patients with high level of BNP the BNP levels decreased after administration of donepezil 116.39 76.58 pg/mL at baseline to 82.24 46.64 pg/mL at first evaluation P 0.011 with the tendency to be reduced in the follow-up period BNP did not change in patients with low level of BNP Donepezil seemed to be safe in patients with dementia without symptomatic heart disease and significantly decreased plasma BNP levels in patients with subclinical chronic heart failure.
ESTHER : Kubo_2012_J.Cardiovasc.Pharmacol_60_310
PubMedSearch : Kubo_2012_J.Cardiovasc.Pharmacol_60_310
PubMedID: 22691879

Title : Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice - Arikawa_2011_PLoS.One_6_e20629
Author(s) : Arikawa M , Kakinuma Y , Handa T , Yamasaki F , Sato T
Ref : PLoS ONE , 6 :e20629 , 2011
Abstract : BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.
ESTHER : Arikawa_2011_PLoS.One_6_e20629
PubMedSearch : Arikawa_2011_PLoS.One_6_e20629
PubMedID: 21750701

Title : Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model - Kakinuma_2010_J.Mol.Cell.Cardiol_48_680
Author(s) : Kakinuma Y , Furihata M , Akiyama T , Arikawa M , Handa T , Katare RG , Sato T
Ref : Journal of Molecular & Cellular Cardiology , 48 :680 , 2010
Abstract : Our recent studies have indicated that acetylcholine (ACh) protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1alpha/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion. These results suggest that a cholinergic system plays a role in modulating angiogenesis. Therefore, we assessed the hypothesis that the cholinergic modulator donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer's disease, exhibits beneficial effects, especially on the acceleration of angiogenesis. We evaluated the effects of donepezil on angiogenic properties in vitro and in vivo, using an ischemic hindlimb model of alpha7 nicotinic receptor-deleted mice (alpha7 KO) and wild-type mice (WT). Donepezil activated angiogenic signals, i.e., HIF-1alpha and VEGF expression, and accelerated tube formation in human umbilical vein endothelial cells (HUVECs). ACh and nicotine upregulated signal transduction with acceleration of tube formation, suggesting that donepezil promotes a common angiogenesis pathway. Moreover, donepezil-treated WT exhibited rich capillaries with enhanced VEGF and PCNA endothelial expression, recovery from impaired tissue perfusion, prevention of ischemia-induced muscular atrophy with sustained surface skin temperature in the limb, and inhibition of apoptosis independent of the alpha7 receptor. Donepezil exerted comparably more effects in alpha7 KO in terms of angiogenesis, tissue perfusion, biochemical markers, and surface skin temperature. Donepezil concomitantly elevated VEGF expression in intracardiac endothelial cells of WT and alpha7 KO and further increased choline acetyltransferase (ChAT) protein expression, which is critical for ACh synthesis in endothelial cells. The present study concludes that donepezil can act as a therapeutic tool to accelerate angiogenesis in cardiovascular disease patients.
ESTHER : Kakinuma_2010_J.Mol.Cell.Cardiol_48_680
PubMedSearch : Kakinuma_2010_J.Mol.Cell.Cardiol_48_680
PubMedID: 19962381

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 : Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium - Kakinuma_2009_FEBS.J_276_5111
Author(s) : Kakinuma Y , Akiyama T , Sato T
Ref : Febs J , 276 :5111 , 2009
Abstract : Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer's disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle, we assessed the hypothesis that ACh is produced by cardiomyocytes, which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase (ChAT) in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy, suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However, with atropine, the basal ACh content was reduced. In response to exogenous ACh or pilocarpine, cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression, and, finally, the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA accelerated cellular energy metabolism, which is suppressed by ACh. Although physostigmine had a minimal effect on the ChAT promoter activity by inhibiting acetylcholinesterase, donepezil resulted in elevation of the activity, protein expression and intracellular ACh level even in the presence of sufficient physostigmine. Orally administered donepezil in mice increased the ChAT promoter activity in a reporter gene-transferred quadriceps femoris muscle and the amount of cardiac ChAT protein. These findings suggest that cardiomyocytes possess an ACh synthesis system, which is positively modulated by cholinergic stimuli. Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles.
ESTHER : Kakinuma_2009_FEBS.J_276_5111
PubMedSearch : Kakinuma_2009_FEBS.J_276_5111
PubMedID: 19674111

Title : Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice - Handa_2009_J.Card.Fail_15_805
Author(s) : Handa T , Katare RG , Kakinuma Y , Arikawa M , Ando M , Sasaguri S , Yamasaki F , Sato T
Ref : J Card Fail , 15 :805 , 2009
Abstract : BACKGROUND: We previously reported that chronic vagal nerve stimulation markedly improved long-term survival after chronic heart failure (CHF) in rats through cardioprotective effects of acetylcholine, independent of the heart rate-slowing mechanism. However, such an approach is invasive and its safety is unknown in clinical settings. To develop an alternative therapy with a clinically available drug, we examined the chronic effect of oral donepezil, an acetylcholinesterase inhibitor against Alzheimer's disease, on cardiac remodeling and survival with a murine model of volume-overloaded CHF. METHODS AND RESULTS: Four weeks after surgery of aortocaval shunt, CHF mice were randomized into untreated and donepezil-treated groups. Donepezil was orally given at a dosage of 5 mgxkg(-1)xday(-1). After 4 weeks of treatment, we evaluated in situ left ventricular (LV) pressure, ex vivo LV pressure-volume relationships, and LV expression of brain natriuretic peptides (BNP). We also observed survival for 50 days. When compared with the untreated group, the donepezil-treated group had significantly low LV end-diastolic pressure, high LV contractility, and low LV expression of BNP. Donepezil significantly reduced the heart weight and markedly improved the survival rate during the 50-day treatment period (54% versus 81%, P < .05). CONCLUSIONS: Oral donepezil improves survival of CHF mice through prevention of pumping failure and cardiac remodeling.
ESTHER : Handa_2009_J.Card.Fail_15_805
PubMedSearch : Handa_2009_J.Card.Fail_15_805
PubMedID: 19879468

Title : Screening enantioselective epoxide hydrolase activities from marine microorganisms: detection of activities in Erythrobacter spp - Hwang_2008_Mar.Biotechnol.(NY)_10_366
Author(s) : Hwang YO , Kang SG , Woo JH , Kwon KK , Sato T , Lee EY , Han MS , Kim SJ
Ref : Mar Biotechnol (NY) , 10 :366 , 2008
Abstract : To develop an enantioselective epoxide hydrolase (EHase) from marine microorganisms, marine samples were collected from a variety of marine environments. Strains isolated by the capability of living on styrene oxide (SO) were screened for retaining enantioselective EHase activities toward SO by combining spectrophotometric, GC, and HPLC analysis. Consequently, one strain, JCS358, was selected, and the sequence analysis of 16S rRNA gene showed that the strain belonged to Erythrobacter cluster. Twelve additional Erythrobacter strains from this study or acquired from culture collections were thereby tested for displaying EHase activities, and most of tested strains showed enantioselective hydrolysis toward SO and glycidyl phenyl ether. Kinetic resolution of racemic SO using whole cell of Erythrobacter sp. JCS358 was performed. Enantiopure (S)-SO could be obtained with an enantiomeric excess (ee) higher than 99% after 15 h incubation. The determination of 1-phenyl-1,2-ethanediol configuration derived from racemic SO confirmed the enantioselective hydrolyzing activity of Erythrobacter sp. JCS358.
ESTHER : Hwang_2008_Mar.Biotechnol.(NY)_10_366
PubMedSearch : Hwang_2008_Mar.Biotechnol.(NY)_10_366
PubMedID: 18214609

Title : Reduced genome of the thioautotrophic intracellular symbiont in a deep-sea clam, Calyptogena okutanii - Kuwahara_2007_Curr.Biol_17_881
Author(s) : Kuwahara H , Yoshida T , Takaki Y , Shimamura S , Nishi S , Harada M , Matsuyama K , Takishita K , Kawato M , Uematsu K , Fujiwara Y , Sato T , Kato C , Kitagawa M , Kato I , Maruyama T
Ref : Current Biology , 17 :881 , 2007
Abstract : Although dense animal communities at hydrothermal vents and cold seeps rely on symbioses with chemoautotrophic bacteria [1, 2], knowledge of the mechanisms underlying these chemosynthetic symbioses is still fragmentary because of the difficulty in culturing the symbionts and the hosts in the laboratory. Deep-sea Calyptogena clams harbor thioautotrophic bacterial symbionts in their gill epithelial cells [1, 2]. They have vestigial digestive tracts and nutritionally depend on their symbionts [3], which are vertically transmitted via eggs [4]. To clarify the symbionts' metabolic roles in the symbiosis and adaptations to intracellular conditions, we present the complete genome sequence of the symbiont of Calyptogena okutanii. The genome is a circular chromosome of 1,022,154 bp with 31.6% guanine + cytosine (G + C) content, and is the smallest reported genome in autotrophic bacteria. It encodes 939 protein-coding genes, including those for thioautotrophy and for the syntheses of almost all amino acids and various cofactors. However, transporters for these substances to the host cell are apparently absent. Genes that are unnecessary for an intracellular lifestyle, as well as some essential genes (e.g., ftsZ for cytokinesis), appear to have been lost from the symbiont genome. Reductive evolution of the genome might be ongoing in the vertically transmitted Calyptogena symbionts.
ESTHER : Kuwahara_2007_Curr.Biol_17_881
PubMedSearch : Kuwahara_2007_Curr.Biol_17_881
PubMedID: 17493812
Gene_locus related to this paper: vesoh-a5cvz2

Title : Altererythrobacter epoxidivorans gen. nov., sp. nov., an epoxide hydrolase-active, mesophilic marine bacterium isolated from cold-seep sediment, and reclassification of Erythrobacter luteolus Yoon et al. 2005 as Altererythrobacter luteolus comb. nov - Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
Author(s) : Kwon KK , Woo JH , Yang SH , Kang JH , Kang SG , Kim SJ , Sato T , Kato C
Ref : Int J Syst Evol Microbiol , 57 :2207 , 2007
Abstract : A novel marine bacterium, strain JCS350(T), was isolated from marine sediment samples collected from a cold-seep area. The 16S rRNA gene sequence of the isolate showed high similarity to that of Erythrobacter luteolus SW-109(T) (95.9 % sequence similarity). Lower 16S rRNA gene sequence similarities were shown to other members of the genus Erythrobacter (94.6-95.4 %) and members of the genus Porphyrobacter (94.5-95.2 %). Phylogenetic analysis with all members of the family Erythrobacteraceae and several members of the family Sphingomonadaceae revealed that the isolate formed a phyletic line with [Erythrobacter] luteolus that was distinct from other members of the family Erythrobacteraceae. The dominant fatty acids of strain JCS350(T) were 18 : 1omega7c, 16 : 1omega7c and cyclopropane 17 : 0. The major respiratory quinone was ubiquinone 10. The DNA G+C content was 54.5 mol%. The isolate did not contain bacteriochlorophyll a. Optimal growth required the presence of 2 % (w/v) NaCl with either 0.18 % CaCl(2) or 0.59 % MgCl(2), at pH 6.5 and at 35 degrees C. On the basis of the evidence of this polyphasic taxonomic study, strain JCS350(T) should be classified in a novel genus and species in the family Erythrobacteraceae, for which the name Altererythrobacter epoxidivorans gen. nov., sp. nov. is proposed. The misclassified species [Erythrobacter] luteolus is transferred to the new genus as Altererythrobacter luteolus comb. nov. The type strain of Altererythrobacter epoxidivorans is JCS350(T) (=KCCM 42314(T) =JCM 13815(T)) and the type strain of Altererythrobacter luteolus is SW-109(T) (=KCTC 12311(T) =JCM 12599(T)).
ESTHER : Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
PubMedSearch : Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
PubMedID: 17911284

Title : The identification of catalytic pentad in the haloalkane dehalogenase DhmA from Mycobacterium avium N85: reaction mechanism and molecular evolution - Pavlova_2007_J.Struct.Biol_157_384
Author(s) : Pavlova M , Klvana M , Jesenska A , Prokop Z , Konecna H , Sato T , Tsuda M , Nagata Y , Damborsky J
Ref : J Struct Biol , 157 :384 , 2007
Abstract : Haloalkane dehalogenase DhmA from Mycobacterium avium N85 showed poor expression and low stability when produced in Escherichia coli. Here, we present expression DhmA in newly constructed pK4RP rhodococcal expression system in a soluble and stable form. Site-directed mutagenesis was used for the identification of a catalytic pentad, which makes up the reaction machinery of all currently known haloalkane dehalogenases. The putative catalytic triad Asp123, His279, Asp250 and the first halide-stabilizing residue Trp124 were deduced from sequence comparisons. The second stabilizing residue Trp164 was predicted from a homology model. Five point mutants in the catalytic pentad were constructed, tested for activity and were found inactive. A two-step reaction mechanism was proposed for DhmA. Evolution of different types of catalytic pentads and molecular adaptation towards the synthetic substrate 1,2-dichloroethane within the protein family is discussed.
ESTHER : Pavlova_2007_J.Struct.Biol_157_384
PubMedSearch : Pavlova_2007_J.Struct.Biol_157_384
PubMedID: 17084094

Title : A C-terminal region of signal peptide peptidase defines a functional domain for intramembrane aspartic protease catalysis - Narayanan_2007_J.Biol.Chem_282_20172
Author(s) : Narayanan S , Sato T , Wolfe MS
Ref : Journal of Biological Chemistry , 282 :20172 , 2007
Abstract : Intramembrane proteolysis is now firmly established as a prominent biological process, and structure elucidation is emerging as the new frontier in the understanding of these novel membrane-embedded enzymes. Reproducing this unusual hydrolysis within otherwise water-excluding transmembrane regions with purified proteins is a challenging prerequisite for such structural studies. Here we show the bacterial expression, purification, and reconstitution of proteolytically active signal peptide peptidase (SPP), a membrane-embedded enzyme in the presenilin family of aspartyl proteases. This finding formally proves that, unlike presenilin, SPP does not require any additional proteins for proteolysis. Surprisingly, the conserved C-terminal half of SPP is sufficient for proteolytic activity; purification and reconstitution of this engineered fragment of several SPP orthologues revealed that this region defines a functional domain for an intramembrane aspartyl protease. The discovery of minimal requirements for intramembrane proteolysis should facilitate mechanistic and structural analysis and help define general biochemical principles of hydrolysis in a hydrophobic environment.
ESTHER : Narayanan_2007_J.Biol.Chem_282_20172
PubMedSearch : Narayanan_2007_J.Biol.Chem_282_20172
PubMedID: 17517891

Title : Donepezil for severe Alzheimer's disease -
Author(s) : Kida Y , Sato T
Ref : Lancet , 368 :361\; author reply 362 , 2006
PubMedID: 16876653

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 : Effect of donepezil on group II mGlu receptor agonist- or antagonist-induced amnesia on passive avoidance in mice - Sato_2003_Neural.Plast_10_319
Author(s) : Sato T , Tanaka K , Ohnishi Y , Irifune M , Nishikawa T
Ref : Neural Plast , 10 :319 , 2003
Abstract : We examined the effect of the acetylcholinesterase (AChE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency. The results suggest that activation of group II mGlu receptors and disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor antagonist) have a negative action on step-through passive avoidance memory performance, and that group II mGlu receptors and ACh interact to modulate learning and memory function.
ESTHER : Sato_2003_Neural.Plast_10_319
PubMedSearch : Sato_2003_Neural.Plast_10_319
PubMedID: 15152985

Title : Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not - Sato_2000_J.Immunol_165_1053
Author(s) : Sato T , Miwa T , Akatsu H , Matsukawa N , Obata K , Okada N , Campbell W , Okada H
Ref : J Immunol , 165 :1053 , 2000
Abstract : Carboxypeptidase R (EC; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity. Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation. CPN, however, previously termed kininase I and anaphylatoxin inactivator, is present in a stable active form in plasma. We report here the isolation of mouse proCPR and CPN cDNA clones that can induce their respective enzymatic activities in culture supernatants of transiently transfected cells. Potato carboxypeptidase inhibitor can inhibit carboxypeptidase activity in culture medium of mouse proCPR-transfected cells. The expression of proCPR mRNA in murine liver is greatly enhanced following LPS injection, whereas CPN mRNA expression remains unaffected. Furthermore, the CPR activity in plasma increased 2-fold at 24 h after LPS treatment. Therefore, proCPR can be considered a type of acute phase protein, whereas CPN is not. An increase in CPR activity may facilitate rapid inactivation of inflammatory mediators generated at the site of Gram-negative bacterial infection and may consequently prevent septic shock. In view of the ability of proCPR to also inhibit fibrinolysis, an excess of proCPR induced by LPS may contribute to hypofibrinolysis in patients suffering from disseminated intravascular coagulation caused by sepsis.
ESTHER : Sato_2000_J.Immunol_165_1053
PubMedSearch : Sato_2000_J.Immunol_165_1053
PubMedID: 10878383

Title : Molecular cloning and partial characterization of rat procarboxypeptidase R and carboxypeptidase N - Kato_2000_Microbiol.Immunol_44_719
Author(s) : Kato T , Akatsu H , Sato T , Matsuo S , Yamamoto T , Campbell W , Hotta N , Okada N , Okada H
Ref : Microbiol Immunol , 44 :719 , 2000
Abstract : Carboxypeptidase R (EC (CPR) and carboxypeptidase N (EC (CPN) cleave carboxy-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Although CPN is present in a stable active form in plasma, CPR is generated from proCPR, a plasma zymogen, by proteolytic enzymes such as thrombin, thrombin-thrombomodulin complex and plasmin. We have isolated rat proCPR and CPN cDNA clones which can induce enzymatic activities in culture supernatants of the transfected cells. mRNA of proCPR was detected only in rat liver by Northern hybridization and showed hepatocyte-specific expression. Expression of proCPR mRNA was enhanced following LPS injection, indicating that proCPR production is increased under inflammatory conditions.
ESTHER : Kato_2000_Microbiol.Immunol_44_719
PubMedSearch : Kato_2000_Microbiol.Immunol_44_719
PubMedID: 11021404

Title : An alternative splicing form of phosphatidylserine-specific phospholipase A1 that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans - Nagai_1999_J.Biol.Chem_274_11053
Author(s) : Nagai Y , Aoki J , Sato T , Amano K , Matsuda Y , Arai H and
Ref : Journal of Biological Chemistry , 274 :11053 , 1999
Abstract : Phosphatidylserine-specific phospholipase A1 (PS-PLA1), which acts specifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to hydrolyze fatty acids at the sn-1 position of these phospholipids, was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In this study we isolated and sequenced cDNA clones encoding human PS-PLA1, which showed 80% homology with rat PS-PLA1 at the amino acid level. In addition to an mRNA encoding a 456-amino acid product (PS-PLA1), an mRNA with four extra bases inserted at the boundary of the exon-intron junction was detected in human tissues and various human cell lines. This mRNA is most probably produced via an alternative use of the 5'-splicing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS-PLA1DeltaC) that lacks two-thirds of the C-terminal domain of PS-PLA1. Unlike PS-PLA1, PS-PLA1DeltaC hydrolyzed exclusively lyso-PS but not PS appreciably. Any other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives were not hydrolyzed at all. These data demonstrated that PS-PLA1DeltaC exhibits lyso-PS-specific lysophospholipase activity and that the C-terminal domain of PS-PLA1 is responsible for recognizing diacylphospholipids. In addition, human PS-PLA1 gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).
ESTHER : Nagai_1999_J.Biol.Chem_274_11053
PubMedSearch : Nagai_1999_J.Biol.Chem_274_11053
PubMedID: 10196188
Gene_locus related to this paper: human-PLA1A

Title : Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate - Nakahara_1998_Am.J.Physiol_275_R541
Author(s) : Nakahara T , Kawada T , Sugimachi M , Miyano H , Sato T , Shishido T , Yoshimura R , Miyashita H , Sunagawa K
Ref : American Journal of Physiology , 275 :R541 , 1998
Abstract : Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.
ESTHER : Nakahara_1998_Am.J.Physiol_275_R541
PubMedSearch : Nakahara_1998_Am.J.Physiol_275_R541
PubMedID: 9688691

Title : Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family - Sato_1997_J.Biol.Chem_272_2192
Author(s) : Sato T , Aoki J , Nagai Y , Dohmae N , Takio K , Doi T , Arai H , Inoue K
Ref : Journal of Biological Chemistry , 272 :2192 , 1997
Abstract : Rat platelets secrete two types of phospholipases upon stimulation; one is type II phospholipase A2 and the other is serine-phospholipid-selective phospholipase A. In the current study we purified serine-phospholipid-selective phospholipase A and cloned its cDNA. The final preparation, purified from extracellular medium of activated rat platelets, gave a 55-kDa protein band on SDS-polyacrylamide gel electrophoresis. [3H]Diisopropyl fluorophosphate, an inhibitor of the enzyme, labeled the 55-kDa protein, suggesting that this polypeptide possesses active serine residues. The cDNA for the enzyme was cloned from a rat megakaryocyte cDNA library. The predicted 456-amino acid sequence contains a putative short N-terminal signal sequence and a GXSXG sequence, which is a motif of an active serine residue of serine esterase. Amino acid sequence homology analysis revealed that the enzyme shares about 30% homology with mammalian lipases (lipoprotein lipase, hepatic lipase, and pancreatic lipase). Regions surrounding the putative active serine, histidine, and aspartic acid, which may form a "lipase triad," were highly conserved among these enzymes. The recombinant protein, which we expressed in Sf9 insect cells using the baculovirus system, hydrolyzed a fatty acyl residue at the sn-1 position of lysophosphatidylserine and phosphatidylserine, but did not appreciably hydrolyze phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, and triglyceride. The present enzyme, named phosphatidylserine-phospholipase A1, is the first phospholipase that exclusively hydrolyses the sn-1 position and has a strict head group specificity for the substrate.
ESTHER : Sato_1997_J.Biol.Chem_272_2192
PubMedSearch : Sato_1997_J.Biol.Chem_272_2192
PubMedID: 8999922
Gene_locus related to this paper: human-PLA1A , ratno-P97535

Title : The complete genome sequence of the gram-positive bacterium Bacillus subtilis - Kunst_1997_Nature_390_249
Author(s) : Kunst F , Ogasawara N , Moszer I , Albertini AM , Alloni G , Azevedo V , Bertero MG , Bessieres P , Bolotin A , Borchert S , Borriss R , Boursier L , Brans A , Braun M , Brignell SC , Bron S , Brouillet S , Bruschi CV , Caldwell B , Capuano V , Carter NM , Choi SK , Cordani JJ , Connerton IF , Cummings NJ , Daniel RA , Denziot F , Devine KM , Dusterhoft A , Ehrlich SD , Emmerson PT , Entian KD , Errington J , Fabret C , Ferrari E , Foulger D , Fritz C , Fujita M , Fujita Y , Fuma S , Galizzi A , Galleron N , Ghim SY , Glaser P , Goffeau A , Golightly EJ , Grandi G , Guiseppi G , Guy BJ , Haga K , Haiech J , Harwood CR , Henaut A , Hilbert H , Holsappel S , Hosono S , Hullo MF , Itaya M , Jones L , Joris B , Karamata D , Kasahara Y , Klaerr-Blanchard M , Klein C , Kobayashi Y , Koetter P , Koningstein G , Krogh S , Kumano M , Kurita K , Lapidus A , Lardinois S , Lauber J , Lazarevic V , Lee SM , Levine A , Liu H , Masuda S , Mauel C , Medigue C , Medina N , Mellado RP , Mizuno M , Moestl D , Nakai S , Noback M , Noone D , O'Reilly M , Ogawa K , Ogiwara A , Oudega B , Park SH , Parro V , Pohl TM , Portelle D , Porwollik S , Prescott AM , Presecan E , Pujic P , Purnelle B , Rapoport G , Rey M , Reynolds S , Rieger M , Rivolta C , Rocha E , Roche B , Rose M , Sadaie Y , Sato T , Scanlan E , Schleich S , Schroeter R , Scoffone F , Sekiguchi J , Sekowska A , Seror SJ , Serror P , Shin BS , Soldo B , Sorokin A , Tacconi E , Takagi T , Takahashi H , Takemaru K , Takeuchi M , Tamakoshi A , Tanaka T , Terpstra P , Togoni A , Tosato V , Uchiyama S , Vandebol M , Vannier F , Vassarotti A , Viari A , Wambutt R , Wedler H , Weitzenegger T , Winters P , Wipat A , Yamamoto H , Yamane K , Yasumoto K , Yata K , Yoshida K , Yoshikawa HF , Zumstein E , Yoshikawa H , Danchin A
Ref : Nature , 390 :249 , 1997
Abstract : Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.
ESTHER : Kunst_1997_Nature_390_249
PubMedSearch : Kunst_1997_Nature_390_249
PubMedID: 9384377
Gene_locus related to this paper: bacsu-CAH , bacsu-cbxnp , bacsu-lip , bacsu-LIPB , bacsu-PKSR , bacsu-pnbae , bacsu-PPSE , bacsu-srf4 , bacsu-srfac , bacsu-YBAC , bacsu-YBDG , bacsu-ybfk , bacsu-ycgS , bacsu-yczh , bacsu-YDEN , bacsu-ydjp , bacsu-yfhM , bacsu-yisY , bacsu-YITV , bacsu-yjau , bacsu-YJCH , bacsu-MHQD , bacsu-yqjl , bacsu-yqkd , bacsu-YRAK , bacsu-YTAP , bacsu-YTMA , bacsu-YTPA , bacsu-ytxm , bacsu-yugF , bacsu-YUII , bacsu-YUKL , bacsu-YVAK , bacsu-YvaM , bacsu-RsbQ

Title : Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the Bacillus subtilis genome containing the skin element and many sporulation genes - Mizuno_1996_Microbiology_142 ( Pt 11)_3103
Author(s) : Mizuno M , Masuda S , Takemaru K , Hosono S , Sato T , Takeuchi M , Kobayashi Y
Ref : Microbiology , 142 ( Pt 11) :3103 , 1996
Abstract : As part of the Bacillus subtilis genome sequencing project, we have determined a 283 kb contiguous sequence from 210 degrees to 232 degrees of the B. subtilis genome. This region contains the 48 kb skin element which is excised during sporulation by a site-specific recombinase. In this region, 310 complete ORFs and one tRNA gene were identified: 66 ORFs have been sequenced and characterized previously by other workers, e.g. acc, ans, bfm, blt, bmr, comE, comG, dnaK, rpoD and sin operons; cwiA, gpr and lysA genes; many sporulation genes and operons, spo0A, spoIIA, spoIIM, spoiiP, spoIIIA, spoIIIC, spoIVB, spoIVCA, spoIVCB and spoVA, etc. The products of 84 ORFs were found to display significant similarity to proteins with known function in data banks, e.g., proteins involved in nucleotide metabolism, lipid biosynthesis, amino acid transport (ABC transporter), phosphate-specific transport, the glycine cleavage system, the two-component regulatory system, cell wall autolysis, ferric uptake and sporulation. However, the functions of more than half of the ORFs (52%, 160 ORFs) are still unknown. In the skin element containing 60 ORFs, 32 ORFs (53%) encode proteins which have significant homology to gene products of the B. subtilis temperate phage phi 105 and/or the defective phage PBSX.
ESTHER : Mizuno_1996_Microbiology_142 ( Pt 11)_3103
PubMedSearch : Mizuno_1996_Microbiology_142 ( Pt 11)_3103
PubMedID: 8969508
Gene_locus related to this paper: bacsu-yqjl , bacsu-yqkd

Title : Kinetic study on the inhibition of acetylcholinesterase by 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (E2020) - Nochi_1995_Biol.Pharm.Bull_18_1145
Author(s) : Nochi S , Asakawa N , Sato T
Ref : Biol Pharm Bull , 18 :1145 , 1995
Abstract : E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride) is currently being developed as a treatment for senile dementia of the Alzheimer type. Its mechanism of action is to increase central cholinergic activity by inhibiting acetylcholinesterase (AChE) in the brain. In this study, the kinetics of the inhibitory action of E2020 on AChE was examined in comparison with its derivatives (2A1050 and 2A1034) and the reference compound tetrahydroaminoacridine (THA) all of which have a similar action. Analysis of the data using Lineweaver-Burk plots shows that inhibition by the test compounds fell into the category of mixed type. Inhibitor dissociation constants for the free enzyme (KI) and acetyl-enzyme (KI) of E2020 are one or two orders of magnitude lower than those of 2A1050, 2A1034 and THA. These findings indicate the strong inhibitory effect of E2020 on AChE.
ESTHER : Nochi_1995_Biol.Pharm.Bull_18_1145
PubMedSearch : Nochi_1995_Biol.Pharm.Bull_18_1145
PubMedID: 8535413