Kato K

References (15)

Title : In vitro acetylcholinesterase inhibitory activity and the antioxidant properties of Aegle marmelos leaf extract: implications for the treatment of Alzheimer's disease - Asaduzzaman_2014_Psychogeriatrics_14_1
Author(s) : Asaduzzaman M , Uddin MJ , Kader MA , Alam AH , Rahman AA , Rashid M , Kato K , Tanaka T , Takeda M , Sadik G
Ref : Psychogeriatrics , 14 :1 , 2014
Abstract : BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by loss of memory and cognition. The effective therapeutic options for AD are limited and thus there is a demand for new drugs. Aegle marmelos (Linn.) (A. marmelos) leaves have been used in traditional medicine to promote intellect and enhance memory. In this study, we evaluated A. marmelos for its acetylcholinesterase (AChE) inhibitory activity and antioxidant property in vitro in the treatment of AD.
METHODS: A crude methanol extract and four fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were prepared from the leaves of A. marmelos. The preparations were assessed for AChE inhibitory activity by the Ellman method, and their antioxidant properties were assessed by several assays: reducing power, scavenging of 1,1-diphenyl-2-picrylhydrazyl free radical and hydroxyl radical, and inhibition of lipid peroxidation. Qualitative and quantitative analyses of endogenous substances in A. marmelos were performed by the standard phytochemical methods.
RESULTS: Among the different extracts tested, the ethyl acetate fraction exhibited the highest inhibition of AChE activity. In the same way, ethyl acetate fraction showed the highest reducing activity and radical scavenging ability towards the 1,1-diphenyl-2-picrylhydrazyl (half maximal inhibitory concentration = 3.84 mug/mL) and hydroxyl free radicals (half maximal inhibitory concentration = 5.68 mug/mL). The antiradical activity of the ethyl acetate fraction appeared to be similar to that of the reference standard butylated hydroxytoluene and catechin used in this study. In addition, the ethyl acetate fraction displayed higher inhibition of brain lipid peroxidation. Phytochemical screening of different extractives of A. marmelos showed the presence of phenols and flavonoids, alkaloid, saponin, glycoside, tannin and steroids. Quantitative analysis revealed higher contents of phenolics (58.79-mg gallic acid equivalent/g dried extract) and flavonoids (375.73-mg gallic acid equivalent/g dried extract) in the ethyl acetate fraction. CONCLUSION: The results suggest that the ethyl acetate fraction of A. marmelos is a significant source of polyphenolic compounds with potential AChE inhibitory property and antioxidant activity and, thus, may be useful in the treatment of AD.
ESTHER : Asaduzzaman_2014_Psychogeriatrics_14_1
PubMedSearch : Asaduzzaman_2014_Psychogeriatrics_14_1
PubMedID: 24646308

Title : Enhancing activity and stability of Burkholderia cepacia lipase by immobilization on surface-functionalized mesoporous silicates - Kato_2010_J.Biosci.Bioeng_109_615
Author(s) : Kato K , Seelan S
Ref : J Biosci Bioeng , 109 :615 , 2010
Abstract : Burkholderia cepacia lipase was immobilized on various types of phenyl-functionalized mesoporous silicates (MPS). MPS, anchored with a phenyl group on the silica wall and with three dimensional (3D) mesoporosity, showed highest lipase adsorption capacity and best activities both in aqueous and organic reagents.
ESTHER : Kato_2010_J.Biosci.Bioeng_109_615
PubMedSearch : Kato_2010_J.Biosci.Bioeng_109_615
PubMedID: 20471602

Title : Enzymatic hydrolysis of structurally diverse phthalic acid esters by porcine and bovine pancreatic cholesterol esterases - Saito_2010_Chemosphere_81_1544
Author(s) : Saito T , Hong P , Tanabe R , Nagai K , Kato K
Ref : Chemosphere , 81 :1544 , 2010
Abstract : A weak hydrolyzing activity against bis (2-ethylhexyl) phthalate (DEHP) was discovered in a commercial crude lipase (EC 3.1.1.3) preparation from porcine pancreas. DEHP was hydrolyzed to mono (2-ethylhexyl) phthalate (MEHP) not by a pancreatic lipase but by a cholesterol esterase (CEase, EC 3.1.1.13), a trace contaminant in the crude lipase preparation. Enzymatic hydrolysis of phthalic acid esters (PAEs), suspected to be endocrine-disrupting chemicals, was investigated using CEases from two species of mammals and a microorganism. Eight structurally diverse PAEs, namely diethyl phthalate (DEP), di-n-propyl phthalate (DPrP), di-n-butyl phthalate (DBP), di-n-pentyl phthalate (DPeP), di-n-hexyl phthalate (DHP), DEHP, n-butyl benzyl phthalate (BBP), and dicyclohexyl phthalate (DCHP), were hydrolyzed to their corresponding monoesters by both porcine and bovine pancreatic CEases, while a microbial CEase from Pseudomonas sp. had no hydrolyzing activity against these PAEs. The hydrolysis experiments with bovine pancreatic CEase (50 U) indicated complete hydrolysis of every PAE (5 mumole) except for BBP and DCHP within 15 min; BBP and DCHP were hydrolyzed within 30 min and 6h, respectively. The rates of PAE hydrolysis could be affected by the bulkiness of alkyl side chains in the PAEs. This study provides important evidence that mammalian pancreatic CEases, such as those from porcine and bovine sources, are potential enzymes for nonspecific degradation of structurally diverse PAEs.
ESTHER : Saito_2010_Chemosphere_81_1544
PubMedSearch : Saito_2010_Chemosphere_81_1544
PubMedID: 20822795
Gene_locus related to this paper: bovin-balip , pig-i3ltk9

Title : Cetilistat (ATL-962), a novel pancreatic lipase inhibitor, ameliorates body weight gain and improves lipid profiles in rats - Yamada_2008_Horm.Metab.Res_40_539
Author(s) : Yamada Y , Kato T , Ogino H , Ashina S , Kato K
Ref : Hormone & Metabolic Research , 40 :539 , 2008
Abstract : Cetilistat is a novel inhibitor of pancreatic lipase. The aim of this report is to evaluate the anti-obesity action of cetilistat in diet-induced obesity (DIO) rats. Cetilistat inhibited rat and human pancreatic lipase activity with an IC (50) of 54.8 nmol/l, and 5.95 nmol/l, respectively, meaning that it is 9.2 times more potent for human pancreatic lipase than for that of rat. Cetilistat was orally administered simultaneously with fat emulsion to Sprague-Dawley rats. Plasma triglyceride (TG) concentrations were measured before and after oral fat loading. The elevation in plasma triglyceride concentration by oral fat loading was reduced by cetilistat in a dose-dependent manner at 3, 10, 30, and 100 mg/kg, indicating that cetilistat reduces intestinal fat absorption in rats. Cetilistat was administered to DIO F344 rats as food admixture in a high-fat diet at 4.9, 14.9, or 50.7 mg/kg/day for three weeks. Both triglyceride and nonesterified fatty acid content in the feces were dose-dependently and drastically increased, suggesting the intestinal breakdown of fat and excretion. Body weight (BW) gain and white adipose tissue (WAT) weight were reduced in a dose-dependent manner. In addition, leptin, TG, and total cholesterol (TC) in plasma were reduced and there were no reports of oily stools. These results suggest that cetilistat ameliorates obesity and hyperlipidemia in DIO rats, a plausible animal model of the most common type of human obesity.
ESTHER : Yamada_2008_Horm.Metab.Res_40_539
PubMedSearch : Yamada_2008_Horm.Metab.Res_40_539
PubMedID: 18500680

Title : Improvement on production of (R)-4-chloro-3-hydroxybutyrate and (S)-3-hydroxy-gamma-butyrolactone with recombinant Escherichia coli cells - Nakagawa_2006_J.Biosci.Bioeng_101_97
Author(s) : Nakagawa A , Idogaki H , Kato K , Shinmyo A , Suzuki T
Ref : J Biosci Bioeng , 101 :97 , 2006
Abstract : (R)-4-Chloro-3-hydroxybutyrate (CHB) and (S)-3-hydroxy-gamma-butyrolactone (HL) are used for the synthesis of biologically and pharmacologically important compounds. Enterobacter sp. DS-S-75 was found to have the unique activity to convert (S)-CHB in the racemate to (S)-HL through asymmetric dechlorination, hydrolysis, and lactonization. As a result, the remaining (R)-CHB and formed (S)-HL could be obtained in a one-pot reaction. We purified the CHB degrading enzyme which catalyzing these reactions and isolated the coding gene from the strain DS-S-75 in order to improve the productivity of these compounds using the transformant. Interestingly, the purified enzyme showed not only dechlorinating, but also hydrolyzing activities on CHB and the similar carboxylic esters, it was then designated CHB hydrolase, and appears to be a novel enzyme. The gene had 1101 bp encoding 367 amino acids including a signal peptide composed of 25 residues. The deduced amino acid sequence contained a conserved region generally found in esterases and lipases, but did not have significant similarity. When asymmetric degradation of racemic methyl CHB (CHBM) was performed using a culture broth of Escherichia coli DH5alpha transformed with the isolated gene, the reaction time was shortened 20-fold over that of the strain DS-S-75, and the maximum concentration of the substrate could be increased from 8% to 15% (w/v). Moreover, both of the obtained residual (R)-CHBM and the formed (S)-HL had high optical purities (>99% e.e.).
ESTHER : Nakagawa_2006_J.Biosci.Bioeng_101_97
PubMedSearch : Nakagawa_2006_J.Biosci.Bioeng_101_97
PubMedID: 16569603
Gene_locus related to this paper: 9entr-q25c43

Title : Biodegradable network elastomeric polyesters from multifunctional aliphatic carboxylic acids and poly(epsilon-caprolactone) diols - Nagata_2006_Macromol.Biosci_6_333
Author(s) : Nagata M , Kato K , Sakai W , Tsutsumi N
Ref : Macromol Biosci , 6 :333 , 2006
Abstract : Biodegradable elastomeric network polyesters were prepared from multifunctional aliphatic carboxylic acids such as tricarballylic acid (Yt) or meso-1,2,3,4-butanetetracarboxylic acid (Xb) and poly(epsilon-caprolactone) (PCL) diols with molecular weights of 530, 1,250 and 2,000 g.mol-1. Prepolymers prepared by a melt polycondensation were cast from DMF solution and postpolymerized at 280 degrees C for various periods of times to form a network. The resultant films were transparent, flexible and insoluble in organic solvents. The network polyesters obtained were characterized by IR absorption spectra, WAXS, density measurement, DSC, and tensile test. YtPCL1250, and XbPCL1250 network polyester films showed good elastomeric properties with high ultimate elongation (540-590%), and low Young's modulus (2.5-3.3 MPa). The enzymatic degradation was estimated by the weight loss of network films in a buffer solution with Rhizopus delemar lipase at 37 degrees C. The degree and rate of degradation were significantly affected by the molecular weight of PCL diol, chemical structures of multifunctional aliphatic carboxylic acids and the morphology of network films. The changes in the solid states of network films during the degradation were also estimated by the results of DSC and WAXS. [see text]
ESTHER : Nagata_2006_Macromol.Biosci_6_333
PubMedSearch : Nagata_2006_Macromol.Biosci_6_333
PubMedID: 16676379

Title : Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats - Kusunoki_2004_Metabolism_53_260
Author(s) : Kusunoki M , Tsutsumi K , Inoue Y , Hara T , Miyata T , Nakamura T , Ogawa H , Sakakibara F , Fukuzawa Y , Okabayashi N , Kato K , Ikeda H , Kurokawa T , Ishikawa T , Otake K , Nakaya Y
Ref : Metabolism , 53 :260 , 2004
Abstract : NO-1886 is a lipoprotein lipase (LPL) activator. Administration of NO-1886 results in an increase in plasma high-density lipoprotein cholesterol (HDL-C) and a decrease in plasma triglyceride (TG) levels. The aim of this study was to ascertain whether NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin (STZ)-induced diabetic rats. Administration of NO-1886 resulted in increased plasma HDL-C levels and decreased TG levels without affecting total cholesterol and glucose levels in the diabetic rats. NO-1886 dose-dependently decreased liver TG contents and cholesterol contents, resulting in improvement of fatty liver. NO-1886 also reduced plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that accompany fatty liver. The liver cholesterol contents were inversely correlated with plasma HDL-C levels (r = -0.5862, P <.001) and were positively correlated with plasma TG levels (r = 0.4083, P <.003). The liver TG contents were inversely correlated with plasma HDL-C levels (r = -0.6195, P <.001) and were positively correlated with plasma TG levels (r = 0.5837, P <.001). There was no correlation between plasma cholesterol levels, and cholesterol and TG contents in liver. These results indicate that reducing plasma TG levels and elevating in HDL-C levels may result in improving fatty liver.
ESTHER : Kusunoki_2004_Metabolism_53_260
PubMedSearch : Kusunoki_2004_Metabolism_53_260
PubMedID: 14767881

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 : Efficient preparation of optically active ketoprofen by Mucor javanicus lipase immobilized on an inorganic support - Kato_2000_J.Biosci.Bioeng_90_332
Author(s) : Kato K , Gong Y , Saito T , Kimoto H
Ref : J Biosci Bioeng , 90 :332 , 2000
Abstract : Lipase M from Mucor javanicus, one of nine commercially available hydrolytic enzymes, showed good enantioselectivity (E=50) for racemic ketoprofen trifluoroethyl ester in phosphate buffer (pH 7.0) containing 30% acetone. Lipase M immobilized on Toyonite 200-A showed the best selectivity (E=55) and reactivity. Moreover, the lipase could be recycled at least 5 times.
ESTHER : Kato_2000_J.Biosci.Bioeng_90_332
PubMedSearch : Kato_2000_J.Biosci.Bioeng_90_332
PubMedID: 16232865

Title : TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons - Kato_1999_Neurosci.Lett_260_5
Author(s) : Kato K , Hayako H , Ishihara Y , Marui S , Iwane M , Miyamoto M
Ref : Neuroscience Letters , 260 :5 , 1999
Abstract : TAK-147, a potent acetylcholinesterase (AChE) inhibitor, potentiated choline acetyltransferase (ChAT) activity in cultured rat septal cholinergic neurons in a concentration-dependent manner with an EC50 value of 4.47 nM. Donepezil, another potent AChE inhibitor, also increased ChAT activity although its potency was less than that of TAK-147. Other AChE inhibitors (rivastigmine, tacrine, physostigmine and neostigmine) showed no effect. The effects of TAK-147 were greater in the presence of NGF, suggesting a synergistic action of TAK-147 and NGF. TAK-147 and donepezil showed high affinity for sigma receptors, whereas tacrine and physostigmine did not. Haloperidol and ifenprodil, high-affinity sigma ligands, potently enhanced ChAT activity in the septal neurons. These results suggest that TAK-147 may have neurotrophic activity on central cholinergic neurons, not via AChE inhibition but possibly via an effect on tau receptors.
ESTHER : Kato_1999_Neurosci.Lett_260_5
PubMedSearch : Kato_1999_Neurosci.Lett_260_5
PubMedID: 10027686

Title : Preparation of optically active trifluoromethylated (3'-indolyl) thiacarboxylic acids, novel plant growth regulators, through lipase-catalyzed enantioselective hydrolysis - Kato_1999_J.Biosci.Bioeng_87_76
Author(s) : Kato K , Tanaka S , Fujii S , Katayama M , Kimoto H
Ref : J Biosci Bioeng , 87 :76 , 1999
Abstract : Among a variety of lipases tested, that obtained from Candida antarctica (SP 435) induced enantioselective hydrolysis of trifluoroethyl 5,5,5-trifluoro-4-(3'-indolyl)-3-thiapentanoate (1c). The selectivity could be increased by optimizing the reaction conditions. Thus, good selectivity was achieved (E = 37) in a buffer containing 10% dichloroethane. In order to improve the optical yields, a sequential kinetic resolution was utilized for the preparative-scale enantioselective hydrolysis of 1c using SP 435. Hydrolysis of trifluoroethyl 6,6,6-trifluoro-5-(3'-indolyl)-4-thiahexanoate (2c) with the lipase of Pseudomonas aeruginosa (LIP) in a buffer containing 20% tert-amyl alcohol at 25 degrees C gave excellent selectivity (E=357).
ESTHER : Kato_1999_J.Biosci.Bioeng_87_76
PubMedSearch : Kato_1999_J.Biosci.Bioeng_87_76
PubMedID: 16232428

Title : Identification of open reading frames in Schizosaccharomyces pombe cDNAs - Yoshioka_1997_DNA.Res_4_363
Author(s) : Yoshioka S , Kato K , Nakai K , Okayama H , Nojima H
Ref : DNA Research , 4 :363 , 1997
Abstract : A total of 214 non-overlapping cDNA clones from Schizosaccharomyces pombe were selected and completely sequenced. The clones not previously reported were divided into the following three groups: 1) homologous to Saccharomyces cerevisiae genes (139 clones); 2) homologous to genes from other organisms but not to those from Sac. cerevisiae (4 clones); and 3) no similar sequences (40 clones). Among the 31 sequences identical to those in the public databases, 4 genes have regions corresponding to introns. Protein sequences which had homologs both in budding yeast and mammals were compared with those from Sac. cerevisiae and mammals. The search revealed that the evolutionary distances among these species are similar at least with genes of this category.
ESTHER : Yoshioka_1997_DNA.Res_4_363
PubMedSearch : Yoshioka_1997_DNA.Res_4_363
PubMedID: 9501991
Gene_locus related to this paper: schpo-SPBC16A3.12C

Title : Neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, in rats - Hirai_1997_J.Pharmacol.Exp.Ther_280_1261
Author(s) : Hirai K , Kato K , Nakayama T , Hayako H , Ishihara Y , Goto G , Miyamoto M
Ref : Journal of Pharmacology & Experimental Therapeutics , 280 :1261 , 1997
Abstract : We examined the neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzaze pin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase (AChE) inhibitor in vitro and in vivo. TAK-147 showed a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC50 = 51.2 nM), and was 3.0- and 2.4-fold more potent than tacrine and physostigmine, respectively. By contrast, TAK-147 was the least potent inhibitor of butyrylcholinesterase activity in rat plasma (IC50 = 23,500 nM). Tacrine and physostigmine inhibited butyrylcholinesterase activity potently and nonselectively. TAK-147 showed a moderate inhibition of muscarinic M1 and M2 receptor binding with K(i) values of 234 and 340 nM, respectively. TAK-147 showed very weak or no inhibition of high-affinity choline uptake, nicotinic receptor binding and choline acetyltransferase activity. In ex vivo experiments, oral administration of TAK-147 at doses ranging from 1 to 10 mg/kg induced a statistically significant and dose-dependent decrease in AChE activity in the cerebral cortex. Of the monoaminergic systems, TAK-147 moderately inhibited uptake of noradrenaline and serotonin with IC50 values of 4020 and 1350 nM, respectively. TAK-147 also inhibited ligand binding at alpha-1, alpha-2 and serotonin 2 receptors with K(i) values of 324, 2330 and 3510 nM, respectively, whereas it showed only weak activities on D1, D2 and serotonin 1A receptor bindings. Oral administration of TAK-147 (3 mg/kg) significantly accelerated the turnover rates of dopamine, noradrenaline and serotonin in the rat brain. These results suggest that TAK-147 activates the central cholinergic system by specific inhibition of AChE activity without affecting peripheral butyrylcholinesterase activity, and that TAK-147 also moderately activates the monoaminergic systems.
ESTHER : Hirai_1997_J.Pharmacol.Exp.Ther_280_1261
PubMedSearch : Hirai_1997_J.Pharmacol.Exp.Ther_280_1261
PubMedID: 9067312

Title : Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 - H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models - Miyamoto_1996_J.Pharmacol.Exp.Ther_277_1292
Author(s) : Miyamoto M , Takahashi H , Kato K , Hirai K , Ishihara Y , Goto G
Ref : Journal of Pharmacology & Experimental Therapeutics , 277 :1292 , 1996
Abstract : We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.
ESTHER : Miyamoto_1996_J.Pharmacol.Exp.Ther_277_1292
PubMedSearch : Miyamoto_1996_J.Pharmacol.Exp.Ther_277_1292
PubMedID: 8667190

Title : Detailed characterization of the biological activities of recombinant human nerve growth factor expressed in Chinese hamster ovary cells - Kakihana_1993_Mol.Chem.Neuropathol_18_51
Author(s) : Kakihana M , Kato K , Fukumoto H , Fujiwara E , Iwane M , Suno M
Ref : Molecular & Chemical Neuropathology , 18 :51 , 1993
Abstract : The biological activities of recombinant human nerve growth factor (rhNGF) produced by Chinese hamster ovary (CHO) cells that were transfected with human NGF gene were investigated in vitro and in vivo. rhNGF showed the same immunoreactivity as mouse NGF (mNGF) in a highly sensitive two-site enzyme immunoassay system employing mouse monoclonal antibody against mouse beta-NGF (MAb 27/21) for both the primary and the secondary antibodies. In PC12 cells, rhNGF promoted neurite extension and induced acetylcholinesterase (AChE) with the same potency as mNGF, showing an ED50 of 10-20 ng/mL. In fetal rat septal neurons cultured on a feeder layer of astroglial cells, rhNGF promoted survival and neurite extension as well as an increase in choline acetyltransferase (ChAT) activity and acetylcholine (ACh) content. At a maximal effective concentration of 30 ng/mL, rhNGF promoted a 1.4-, 2.8-, and 4-fold increase in surviving cell number, ACh content, and ChAT activity, respectively. rhNGF was five times more potent than mNGF for the increase in ChAT activity and ACh content showing an ED50 of 0.5 ng/mL, although the maximal response was the same for the two NGFs. Transection of the fimbria-fornix resulted in a loss of AChE-positive cells in the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB). The administration of rhNGF or mNGF (3 or 30 micrograms in gel form) attenuated the loss of AChE-positive cells; rhNGF was as potent as or even more potent than mNGF. Radio frequency lesion of the basal forebrain (BF) including the nucleus basalis magnocellularis (NBM) resulted in severe impairment of memory and/or learning in passive avoidance and Morris' water maze tasks. Repeated injection of rhNGF (5 micrograms x 5 over 2 wk) into the lateral ventricle ameliorated the behavioral impairment in the water maze task but not in passive avoidance. rhNGF treatment increased ChAT activity in the frontal cortex and even in other subregions of the cerebral cortex where ChAT activity was not decreased by BF lesion. These results indicate that human NGF can be measured in an enzyme immunoassay system using monoclonal antibody against mNGF (MAb 27/21) and that rhNGF has potent biological activity, comparable to or greater than mNGF, both in vitro and in vivo.
ESTHER : Kakihana_1993_Mol.Chem.Neuropathol_18_51
PubMedSearch : Kakihana_1993_Mol.Chem.Neuropathol_18_51
PubMedID: 8466595