Fujikawa Y

References (4)

Title : Fluorescein diacetate (FDA) and its analogue as substrates for Pi-class glutathione S-transferase (GSTP1) and their biological application - Fujikawa_2018_Talanta_179_845
Author(s) : Fujikawa Y , Nampo T , Mori M , Kikkawa M , Inoue H
Ref : Talanta , 179 :845 , 2018
Abstract : Pi class glutathione S-transferase (GSTP1) is highly expressed in various cancerous cells and pre-neoplastic legions, where it is involved in apoptotic resistance or metabolism of several anti-tumour chemotherapeutics. Therefore, GSTP1 is a marker of malignant and pre-malignant cells and is a promising target for visualization and drug development. Here we demonstrate that fluorescein diacetate (FDA), a fluorescent probe used for vital staining, is a fluorescently activated by esterolytic activity of human GSTP1 (hGSTP1) selectively among various cytosolic GSTs. Fluorescence activation of FDA susceptible to GST inhibitors was observed in MCF7 cells exogenously overexpressing hGSTP1, but not in cells overexpressing hGSTA1 or hGSTM1. Inhibitor-sensitive fluorescence activation was also observed in several cancer cell lines endogenously expressing GSTP1, suggesting that GSTP1 is involved in FDA esterolysis in these cells. Among the FDA derivatives examined, FOMe-Ac, the acetyl ester of fluorescein O-methyl ether, was found to be a potential reporter for GSH-dependent GSTP1 activity as well as for carboxylesterase activity. Since GSTP1 is highly expressed in various types of cancer cells compared to their normal counterparts, improving the fluorogenic substrates to be more selective to the esterolysis activity of GSTP1 rather than carboxylesterases should lead to development of tools for detecting GSTP1-overexpressing cancer cells and investigating the biological functions of GSTP1.
ESTHER : Fujikawa_2018_Talanta_179_845
PubMedSearch : Fujikawa_2018_Talanta_179_845
PubMedID: 29310316

Title : Galantamine-induced amyloid-{beta} clearance mediated via stimulation of microglial nicotinic acetylcholine receptors - Takata_2010_J.Biol.Chem_285_40180
Author(s) : Takata K , Kitamura Y , Saeki M , Terada M , Kagitani S , Kitamura R , Fujikawa Y , Maelicke A , Tomimoto H , Taniguchi T , Shimohama S
Ref : Journal of Biological Chemistry , 285 :40180 , 2010
Abstract : Reduction of brain amyloid-beta (Abeta) has been proposed as a therapeutic target for Alzheimer disease (AD), and microglial Abeta phagocytosis is noted as an Abeta clearance system in brains. Galantamine is an acetylcholinesterase inhibitor approved for symptomatic treatment of AD. Galantamine also acts as an allosterically potentiating ligand (APL) for nicotinic acetylcholine receptors (nAChRs). APL-binding site is located close to but distinct from that for acetylcholine on nAChRs, and FK1 antibody specifically binds to the APL-binding site without interfering with the acetylcholine-binding site. We found that in human AD brain, microglia accumulated on Abeta deposits and expressed alpha7 nAChRs including the APL-binding site recognized with FK1 antibody. Treatment of rat microglia with galantamine significantly enhanced microglial Abeta phagocytosis, and acetylcholine competitive antagonists as well as FK1 antibody inhibited the enhancement. Thus, the galantamine-enhanced microglial Abeta phagocytosis required the combined actions of an acetylcholine competitive agonist and the APL for nAChRs. Indeed, depletion of choline, an acetylcholine-competitive alpha7 nAChR agonist, from the culture medium impeded the enhancement. Similarly, Ca(2+) depletion or inhibition of the calmodulin-dependent pathways for the actin reorganization abolished the enhancement. These results suggest that galantamine sensitizes microglial alpha7 nAChRs to choline and induces Ca(2+) influx into microglia. The Ca(2+)-induced intracellular signaling cascades may then stimulate Abeta phagocytosis through the actin reorganization. We further demonstrated that galantamine treatment facilitated Abeta clearance in brains of rodent AD models. In conclusion, we propose a further advantage of galantamine in clinical AD treatment and microglial nAChRs as a new therapeutic target.
ESTHER : Takata_2010_J.Biol.Chem_285_40180
PubMedSearch : Takata_2010_J.Biol.Chem_285_40180
PubMedID: 20947502

Title : Extremely sensitive biomarker of acute organophosphorus insecticide exposure - Fujikawa_2005_Hum.Exp.Toxicol_24_333
Author(s) : Fujikawa Y , Satoh T , Suganuma A , Suzuki S , Niikura Y , Yui S , Yamaura Y
Ref : Hum Exp Toxicol , 24 :333 , 2005
Abstract : Egasyn-beta-glucuronidase complex is located at the luminal site of liver microsomal endoplasmic reticulum. When organophosphorus insecticides (OP) are incorporated into the liver microsomes, they become tightly bound to egasyn, a carboxylesterase isozyme, and subsequently, beta-glucuronidase (BG) is dissociated and released into blood. Consequently, the increase in plasma BG activity becomes a good biomarker of OP exposure. Thus, the single administration of EPN (O-ethyl O-p-nitrophenylphenylphosphonothioate), acephate and chlorpyrifos increased plasma BG activity in approximately 100-fold the control level in rats. The increase in plasma BG activity after OP exposure is a much more sensitive biomarker of acute OP exposure than acetylcholinesterase (AChE) inhibition.
ESTHER : Fujikawa_2005_Hum.Exp.Toxicol_24_333
PubMedSearch : Fujikawa_2005_Hum.Exp.Toxicol_24_333
PubMedID: 16004201
Gene_locus related to this paper: human-CES1 , mouse-Ces1e , ratno-Ces1e

Title : Nootropic candidates inhibit head-twitches induced by mescaline in mice - Yamamoto_1992_Jpn.J.Pharmacol_59_419
Author(s) : Yamamoto T , Ohno M , Yatsugi S , Fujikawa Y , Ueki S
Ref : Japanese Journal of Pharmacology , 59 :419 , 1992
Abstract : The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches.
ESTHER : Yamamoto_1992_Jpn.J.Pharmacol_59_419
PubMedSearch : Yamamoto_1992_Jpn.J.Pharmacol_59_419
PubMedID: 1434136