Okabe S

References (10)

Title : Hybrid pharmacophore design and synthesis of donepezil-inspired aurone derivative salts as multifunctional acetylcholinesterase inhibitors - Funahashi_2024_Bioorg.Chem_145_107229
Author(s) : Funahashi R , Matsuura F , Ninomiya M , Okabe S , Takashima S , Tanaka K , Nishina A , Koketsu M
Ref : Bioorg Chem , 145 :107229 , 2024
Abstract : Flavonoids, a ubiquitous group of plant polyphenols, are well-known for their beneficial effects on human health. Their phenylchromane skeletons have structural similarities to donepezil [the US FDA-approved drug used to treat Alzheimer's disease (AD)]. The objective of this study was to design and synthesize valuable agents derived from flavonoids for relieving the symptoms of AD. A variety of flavonoid derivative salts incorporating benzylpyridinium units were synthesized and several of them remarkedly inhibited acetylcholinesterase (AChE) activity in vitro. Additionally, aurone derivative salts protected against cell death resulting from t-BHP exposure in rat pheochromocytoma PC12 cells and slightly promoted neurite outgrowth. Furthermore, they potently suppressed the aggregation of amyloid-beta (Abeta(1-42)). Our findings highlight the effectiveness of donepezil-inspired aurone derivative salts as multipotent candidates for AD.
ESTHER : Funahashi_2024_Bioorg.Chem_145_107229
PubMedSearch : Funahashi_2024_Bioorg.Chem_145_107229
PubMedID: 38401360

Title : Desmethyl type germinone, a specific agonist for the HTL\/KAI2 receptor, induces the Arabidopsis seed germination in a gibberellin-independent manner - Okabe_2023_Biochem.Biophys.Res.Commun_649_110
Author(s) : Okabe S , Kitaoka K , Suzuki T , Kuruma M , Hagihara S , Yamaguchi S , Fukui K , Seto Y
Ref : Biochemical & Biophysical Research Communications , 649 :110 , 2023
Abstract : DWARF14 (D14) and HTL/KAI2 (KAI2) are paralogous receptors in the alpha/beta-hydrolase superfamily. D14 is the receptor for a class of plant hormones, strigolactones (SLs), and KAI2 is the receptor for the smoke-derived seed germination inducer, Karrikin (KAR), in Arabidopsis. Germinone (Ger) was previously reported as a KAI2 agonist with germination-inducing activity for thermo-inhibited Arabidopsis seed. However, Ger was not specific to KAI2, and could also bind to D14. It was reported that SL analogs with a desmethyl-type D-ring structure are specifically recognized by KAI2. On the basis of this observation, we synthesized a desmethyl-type germinone (dMGer). We found that dMGer is highly specific to KAI2. Moreover, dMGer induced Arabidopsis seed germination more effectively than did Ger. In addition, dMGer induced the seed germination of Arabidopsis in a manner independently of GA, a well-known germination inducer in plants.
ESTHER : Okabe_2023_Biochem.Biophys.Res.Commun_649_110
PubMedSearch : Okabe_2023_Biochem.Biophys.Res.Commun_649_110
PubMedID: 36764113

Title : A Divergent Clade KAI2 Protein in the Root Parasitic Plant Orobanche minor Is a Highly Sensitive Strigolactone Receptor and Is Involved in the Perception of Sesquiterpene Lactones - Takei_2023_Plant.Cell.Physiol__
Author(s) : Takei S , Uchiyama Y , Burger M , Suzuki T , Okabe S , Chory J , Seto Y
Ref : Plant Cell Physiol , : , 2023
Abstract : Strigolactones (SLs) were initially discovered as germination inducers for root parasitic plants. In 2015, three groups independently reported the characterization of the SL receptor in the root parasitic plant Striga hermonthica, which causes significant damage to crop production, particularly in sub-Saharan Africa. The characterized receptors belong to HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 (HTL/KAI2), which is a member of the alpha/beta-hydrolase protein superfamily. In non-parasitic plants, HTL/KAI2 perceives the smoke-derived germination inducer karrikin and a yet-unidentified endogenous ligand. However, root parasitic plants evolved a specific clade of HTL/KAI2 that has diverged from the KAI2 clade of non-parasitic plants. The S. hermonthica SL receptors are included in this specific clade, which is called KAI2 divergent (KAI2d). Orobanche minor is an obligate root holoparasitic plant that grows completely dependent on the host for water and nutrients because of a lack of photosynthetic ability. Previous phylogenetic analysis of KAI2 proteins in O. minor has demonstrated the presence of at least five KAI2d clade genes. Here, we report that KAI2d3 and KAI2d4 in O. minor have the ability to act as the SL receptors. They directly interact with SLs in vitro, and when expressed in Arabidopsis, they rescue thermo-inhibited germination in response to the synthetic SL analog GR24. In particular, KAI2d3 showed high sensitivity to GR24 when expressed in Arabidopsis, suggesting that this receptor enables highly sensitive SL recognition in O. minor. Furthermore, we provide evidence that these KAI2d receptors are involved in the perception of sesquiterpene lactones, non-strigolactone-type germination inducers.
ESTHER : Takei_2023_Plant.Cell.Physiol__
PubMedSearch : Takei_2023_Plant.Cell.Physiol__
PubMedID: 37061839
Gene_locus related to this paper: oromi-OmKAI2d3 , oromi-OmKAI2c , oromi-OmKAI2d5 , oromi-OmKAI2d2 , oromi-OmKAI2d1 , oromi-OmD14 , oromi-OmKAI2d4

Title : Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice - Yoshida_2021_Nat.Commun_12_1848
Author(s) : Yoshida T , Yamagata A , Imai A , Kim J , Izumi H , Nakashima S , Shiroshima T , Maeda A , Iwasawa-Okamoto S , Azechi K , Osaka F , Saitoh T , Maenaka K , Shimada T , Fukata Y , Fukata M , Matsumoto J , Nishijo H , Takao K , Tanaka S , Okabe S , Tabuchi K , Uemura T , Mishina M , Mori H , Fukai S
Ref : Nat Commun , 12 :1848 , 2021
Abstract : Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase delta (PTPdelta) splice variants, competing with NRXN binding. NLGN3-PTPdelta complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPdelta and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPdelta interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.
ESTHER : Yoshida_2021_Nat.Commun_12_1848
PubMedSearch : Yoshida_2021_Nat.Commun_12_1848
PubMedID: 33758193
Gene_locus related to this paper: mouse-3neur

Title : Draft Genome Sequence of an Anaerobic Ammonium-Oxidizing Bacterium, "\;Candidatus Brocadia sinica" - Oshiki_2015_Genome.Announc_3_e00267
Author(s) : Oshiki M , Shinyako-Hata K , Satoh H , Okabe S
Ref : Genome Announc , 3 : , 2015
Abstract : A draft genome sequence of an anaerobic ammonium-oxidizing (anammox) bacterium, "Candidatus Brocadia sinica," was determined by pyrosequencing and by screening a fosmid library. A 4.07-Mb genome sequence comprising 3 contigs was assembled, in which 3,912 gene-coding regions, 47 tRNAs, and a single rrn operon were annotated.
ESTHER : Oshiki_2015_Genome.Announc_3_e00267
PubMedSearch : Oshiki_2015_Genome.Announc_3_e00267
PubMedID: 25883286
Gene_locus related to this paper: 9bact-a0a0c9q7s9

Title : Enhanced synapse remodelling as a common phenotype in mouse models of autism - Isshiki_2014_Nat.Commun_5_4742
Author(s) : Isshiki M , Tanaka S , Kuriu T , Tabuchi K , Takumi T , Okabe S
Ref : Nat Commun , 5 :4742 , 2014
Abstract : Developmental deficits in neuronal connectivity are considered to be present in patients with autism spectrum disorders (ASDs). Here we examine this possibility by using in vivo spine imaging in the early postnatal cortex of ASD mouse models. Spines are classified by the presence of either the excitatory postsynaptic marker PSD-95 or the inhibitory postsynaptic marker gephyrin. ASD mouse models show consistent upregulation in the dynamics of PSD-95-positive spines, which may subsequently contribute to stable synaptic connectivity. In contrast, spines receiving inputs from the thalamus, detected by the presence of gephyrin clusters, are larger, highly stable and unaffected in ASD mouse models. Importantly, two distinct mouse models, human 15q11-13 duplication and neuroligin-3 R451C point mutation, show highly similar phenotypes in spine dynamics. This selective impairment in dynamics of PSD-95-positive spines receiving intracortical projections may be a core component of early pathological changes and be a potential target of early intervention.
ESTHER : Isshiki_2014_Nat.Commun_5_4742
PubMedSearch : Isshiki_2014_Nat.Commun_5_4742
PubMedID: 25144834

Title : Neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity - Takada-Takatori_2006_Eur.J.Pharmacol_549_19
Author(s) : Takada-Takatori Y , Kume T , Sugimoto M , Katsuki H , Niidome T , Sugimoto H , Fujii T , Okabe S , Akaike A
Ref : European Journal of Pharmacology , 549 :19 , 2006
Abstract : We examined the mechanisms of the neuroprotective effects of two central-type acetylcholinesterase inhibitors, galanthamine and tacrine, on nitric oxide-mediated glutamate neurotoxicity using primary cultures from the cerebral cortex of fetal rats. Galanthamine and tacrine showed prominent protective effects against glutamate neurotoxicity. Mecamylamine, a nicotinic acetylcholine receptor antagonist, but not scopolamine, a muscarinic acetylcholine receptor antagonist, inhibited the protective effects of these inhibitors on glutamate neurotoxicity. Furthermore, dihydro-beta-erythroidine, an alpha4-nicotinic receptor antagonist, and methyllycaconitine, an alpha7-nicotinic receptor antagonist, inhibited the neuroprotective effects of galanthamine but not tacrine. Next, we investigated the site of action where galanthamine and tacrine prevent glutamate neurotoxicity. Both these acetylcholinesterase inhibitors prevented glutamate- and ionomycin-induced neurotoxicity, but only tacrine prevented S-nitrosocysteine-induced neurotoxicity. These results suggest that galanthamine and tacrine protect cortical neurons from glutamate neurotoxicity via different mechanisms.
ESTHER : Takada-Takatori_2006_Eur.J.Pharmacol_549_19
PubMedSearch : Takada-Takatori_2006_Eur.J.Pharmacol_549_19
PubMedID: 16996497

Title : Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography - Kimura_2005_Ind.Health_43_285
Author(s) : Kimura K , Yokoyama K , Sato H , Nordin RB , Naing L , Kimura S , Okabe S , Maeno T , Kobayashi Y , Kitamura F , Araki S
Ref : Ind Health , 43 :285 , 2005
Abstract : We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.
ESTHER : Kimura_2005_Ind.Health_43_285
PubMedSearch : Kimura_2005_Ind.Health_43_285
PubMedID: 15895843

Title : Gastric acid secretion in L-histidine decarboxylase-deficient mice - Tanaka_2002_Gastroenterology_122_145
Author(s) : Tanaka S , Hamada K , Yamada N , Sugita Y , Tonai S , Hunyady B , Palkovits M , Falus A , Watanabe T , Okabe S , Ohtsu H , Ichikawa A , Nagy A
Ref : Gastroenterology , 122 :145 , 2002
Abstract : BACKGROUND & AIMS: Histamine, gastrin, and acetylcholine are known to be the primary secretagogues of gastric acid secretion, but how the roles are shared among these secretagogues remains to be fully clarified. To evaluate the cooperation between histamine and the other secretagogues, acid secretion responses induced by each secretagogue were measured in L-histidine decarboxylase (HDC)-deficient mice.
METHODS: Acid secretion was measured by the titration of acid under anesthesia. The expression of selected genes involved in acid secretion was determined by Northern blot and/or immunoblot analysis. Histamine-2 (H(2)) receptor binding in the gastric mucosa was investigated using [(3)H]tiotidine.
RESULTS: HDC-deficient mice showed low basal and high exogenous histamine-stimulated acid secretion. The mutant mice showed hypergastrinemia and did not undergo acid secretion upon treatment with exogenous gastrin. However, carbachol stimulated weak and transient acid secretion in the mutants. The Bmax values for H(2) and the expression of Gs alpha in gastric mucosal membranes were higher in the mutants than in the wild-type mice.
CONCLUSIONS: This study confirms the concept that histamine production is essential for gastric acid secretion induced by gastrin, but not for that induced by carbachol. HDC-deficient mice should be a suitable model for further functional analyses of the correlation between histamine and the other acid secretagogues.
ESTHER : Tanaka_2002_Gastroenterology_122_145
PubMedSearch : Tanaka_2002_Gastroenterology_122_145
PubMedID: 11781289

Title : Pharmacological aspects of acid secretion - Hirschowitz_1995_Dig.Dis.Sci_40_3S
Author(s) : Hirschowitz BI , Keeling D , Lewin M , Okabe S , Parsons M , Sewing K , Wallmark B , Sachs G
Ref : Digestive Diseases & Sciences , 40 :3S , 1995
Abstract : The secretion of gastric acid is regulated both centrally and peripherally. The finding that H2-receptor antagonists are able to reduce or abolish acid secretion due to vagal, gastrinergic, and histaminergic stimulation shows that histamine plays a pivotal role in stimulation of the parietal cell. In the rat, the fundic histamine is released from the ECL cell, in response to gastrin, acetylcholine, or epinephrine, and histamine release is inhibited by somatostatin or by the H3-receptor ligand, R-alpha-methyl histamine. The parietal cell has a muscarinic, M3, receptor responsible for [Ca]i regulation. Blockade of muscarinic receptors by atropine can be as effective as H2-receptor blockade in controlling acid secretion. However, general effects on muscarinic receptors elsewhere produce significant side effects. The different receptor pathways converge to stimulate the gastric H+,K(+)-ATPase, the pump responsible for acid secretion by the stomach. This enzyme is an alpha,beta heterodimer, present in cytoplasmic membrane vesicles of the resting cell and in the canaliculus of the stimulated cell. It has been shown that acid secretion by the pump depends on provision of K+Cl- efflux pathway becoming associated with the pump. As secretion occurs only in the canaliculus, this K+Cl- pathway is activated only when the pump inserts into the canalicular membrane. Transport by the enzyme involves reciprocal conformational changes in the cytoplasmic and extracytoplasmic domain. These result in changes in sidedness and affinity for H3O+ and K+, enabling active H+ for K+ exchange. The acid pump inhibitors of the substituted benzimidazole class, such as omeprazole, are concentrated in the canaliculus of the secreting parietal cell and are activated there to form sulfenamides. The omeprazole sulfenamide, for example, reacts covalently with two cysteines in the extracytoplasmic loops between the fifth and sixth transmembrane and the seventh and eighth transmembrane segments of the alpha subunit of the H+,K(+)-ATPase, forming disulfide derivatives. This inhibits ATP hydrolysis and H+ transport, resulting in effective, long-lasting regulation of acid secretion. Therefore, this class of acid pump inhibitor is significantly more effective and faster acting than the H2 receptor antagonists. K+ competitive antagonists bind to the M1 and M2 transmembrane segments of the alpha subunit of the acid pump and also abolish ATPase activity. These drugs should also be able to reduce acid secretion more effectively than receptor antagonists and provide shorter acting but complete inhibition of acid secretion.
ESTHER : Hirschowitz_1995_Dig.Dis.Sci_40_3S
PubMedSearch : Hirschowitz_1995_Dig.Dis.Sci_40_3S
PubMedID: 7859583