Takada K

References (7)

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 : Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: A special reference to the nested gene LYNX1 - Moriwaki_2015_Int.Immunopharmacol_29(1)_71
Author(s) : Moriwaki Y , Takada K , Tsuji S , Kawashima K , Misawa H
Ref : Int Immunopharmacol , 29 :71 , 2015
Abstract : A novel nicotinic acetylcholine (ACh) receptor (nAChR)-mediated transduction pathway, regulating keratinocyte function, has been elucidated in studies of secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein (SLURP)-1 and -2. SLURPs are members of Ly6/neurotoxin superfamily (Ly6SF) of proteins containing the unique three-finger domain in their three-dimensional structure. Some endogenously expressed Ly6SF proteins (such as LYNX1, SLURP-1, and SLURP-2) modulate the function of nAChR, either as allosteric and/or orthosteric modulators, or as antagonists. Although the expression and functions of SLURP-1 and SLURP-2 in keratinocytes are well documented, the expression and the modes of action of LYNX1 in keratinocytes are unknown. Additionally, a particular hybrid transcript, LYNX1-SLURP2, which contains both LYNX1 and SLURP-2 sequences, with unknown function, has been reported. Furthermore, although SLURP2 is a gene strongly induced in psoriatic skin lesions, the mechanisms controlling SLURP2 expression are largely unknown. To better understand the function of nAChRs in keratinocytes, we investigated the expression profiles of LYNX1, LYNX1-SLURP-2, and SLURP-2 in keratinocytes under various inflammatory conditions. We found that keratinocytes express LYNX1 and SLURP2, but not LYNX1-SLURP2, at mRNA and protein levels. IL-22 treatment increased SLURP2 expression in keratinocytes, but this effect was completely abolished by IFN-gamma. Furthermore, the IL-22-induced up-regulation of SLURP2 was completely suppressed by the inhibitor or siRNA for STAT3, a major transcriptional factor downstream of IL-22. These findings provide new insights into the nAChR-mediated regulatory mechanism of SLURP-2 expression in keratinocytes.
ESTHER : Moriwaki_2015_Int.Immunopharmacol_29(1)_71
PubMedSearch : Moriwaki_2015_Int.Immunopharmacol_29(1)_71
PubMedID: 26033490

Title : An environmental bacterial taxon with a large and distinct metabolic repertoire - Wilson_2014_Nature_506_58
Author(s) : Wilson MC , Mori T , Ruckert C , Uria AR , Helf MJ , Takada K , Gernert C , Steffens UA , Heycke N , Schmitt S , Rinke C , Helfrich EJ , Brachmann AO , Gurgui C , Wakimoto T , Kracht M , Crusemann M , Hentschel U , Abe I , Matsunaga S , Kalinowski J , Takeyama H , Piel J
Ref : Nature , 506 :58 , 2014
Abstract : Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.
ESTHER : Wilson_2014_Nature_506_58
PubMedSearch : Wilson_2014_Nature_506_58
PubMedID: 24476823
Gene_locus related to this paper: 9delt-w4lci7 , 9delt-w4lkq9 , 9delt-w4lj58 , 9delt-w4l7a4 , 9delt-w4m617

Title : Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine - Miyata_2008_Ann.N.Y.Acad.Sci_1139_458
Author(s) : Miyata H , Hironaka N , Takada K , Miyasato K , Nakamura K , Yanagita T
Ref : Annals of the New York Academy of Sciences , 1139 :458 , 2008
Abstract : The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.
ESTHER : Miyata_2008_Ann.N.Y.Acad.Sci_1139_458
PubMedSearch : Miyata_2008_Ann.N.Y.Acad.Sci_1139_458
PubMedID: 18991893

Title : [Alterrations in neurotransmitter, amino acid and free radical related substances in cerebrospinal fluid in patients with cerebrovascular diseases] - Egashira_1999_Nippon.Ronen.Igakkai.Zasshi_36_256
Author(s) : Egashira T , Goto H , Takeda H , Takada K , Matsumiya T
Ref : Nippon Ronen Igakkai Zasshi , 36 :256 , 1999
Abstract : Acetylcholinesterase (AChE), choline, monoamine and its metabolite, amino acid and superoxide dismutase (SOD) levels were measured in cerebrospinal fluid (CSF) in patients with cerebrovascular diseases. Patients were classified into the following four groups; controls: normal subjects without neurological disease, group A: cerebral hemorrhage, group B: cerebral infarction, group C: patients with mental impairment, including those in groups A and B, and a low score on Hasegawa's Dementia Rating Scale. CSF AChE level of groups A, B and C was decreased significantly, while choline concentration from patients showed a increase compared with that of control cases. CSF alanine concentration showed a tendency to increase, while glycine and glutamate tended to decrease. CSF epinephrine, norepinephrine or 3-methoxy-4-hydroxyphenylethylen glycol concentrations of groups A, B and C did not exhibit a significant difference from that in control cases. Some cases with cerebrovascular diseases showed low concentrations of both CSF 5-hydroxyindole acetic acid and homovanillic acid. However, dihydroxyphenyl acetic acid concentration was higher than in control cases. The CSF SOD level was not significantly from that in control cases. The changes in neurochemical substances in the CSF support their use as markers of cerebrovascular disease-related change.
ESTHER : Egashira_1999_Nippon.Ronen.Igakkai.Zasshi_36_256
PubMedSearch : Egashira_1999_Nippon.Ronen.Igakkai.Zasshi_36_256
PubMedID: 10410569

Title : Reinforcing effect as a function of infusion speed in intravenous self-administration of nicotine in rhesus monkeys - Wakasa_1995_Nihon.Shinkei.Seishin.Yakurigaku.Zasshi_15_53
Author(s) : Wakasa Y , Takada K , Yanagita T
Ref : Nihon Shinkei Seishin Yakurigaku Zasshi , 15 :53 , 1995
Abstract : The influence of infusion speed on the reinforcing effect of nicotine (NIC) 30 micrograms/kg/infusion was studied in rhesus monkeys using intravenous self-administration at infusion speeds of 5.2, 1.3, and 0.3 micrograms/s under a fixed-ratio 5 schedule with a 15-min time-out after each intake. The 24-h self-administration rate was observed in 3 periods of 8 days each for each speed, separated by saline self-administration periods of 2 weeks each. As a result, when a fixed infusion speed of 5.2 micrograms/s was used throughout the 3 periods, the average rates of NIC were not significantly different each other, but when the infusion speed was changed from 5.2 to 1.3, and then to 0.3 micrograms/s, the average rates significantly decreased. The plasma level following a single-dose infusion of NIC 30 micrograms/kg positively correlated with the infusion speeds. These results indicate that the reinforcing effect of NIC is a function of the infusion speed, most likely through elevation of the peak level of NIC in the plasma.
ESTHER : Wakasa_1995_Nihon.Shinkei.Seishin.Yakurigaku.Zasshi_15_53
PubMedSearch : Wakasa_1995_Nihon.Shinkei.Seishin.Yakurigaku.Zasshi_15_53
PubMedID: 7750017

Title : Psychopharmacological studies on nicotine and tobacco smoking in rhesus monkeys -
Author(s) : Yanagita T , Ando K , Kato S , Takada K
Ref : Psychopharmacol Bull , 19 :409 , 1983
PubMedID: 6635115