Okada H

References (10)

Title : Functional involvement of endothelial lipase in hepatitis B virus infection - Shirasaki_2023_Hepatol.Commun_7_e0206
Author(s) : Shirasaki T , Murai K , Ishida A , Kuroki K , Kawaguchi K , Wang Y , Yamanaka S , Yasukawa R , Kawasaki N , Li YY , Shimakami T , Sumiyadorj A , Nio K , Sugimoto S , Orita N , Takayama H , Okada H , Thi Bich PD , Iwabuchi S , Hashimoto S , Ide M , Tabata N , Ito S , Matsushima K , Yanagawa H , Yamashita T , Kaneko S , Honda M
Ref : Hepatol Commun , 7 :e0206 , 2023
Abstract : BACKGROUND: HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence. METHODS: The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane. RESULTS: We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells. CONCLUSIONS: LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity.
ESTHER : Shirasaki_2023_Hepatol.Commun_7_e0206
PubMedSearch : Shirasaki_2023_Hepatol.Commun_7_e0206
PubMedID: 37655967
Gene_locus related to this paper: human-LIPG

Title : EP2 and EP3 receptors as therapeutic targets for underactive bladder\/detrusor underactivity due to diabetic cystopathy in a type 1 diabetic rat model - Sekido_2020_Low.Urin.Tract.Symptoms__
Author(s) : Sekido N , Otsuki T , Kida J , Mashimo H , Wakamatsu D , Okada H , Matsuya H
Ref : Low Urin Tract Symptoms , : , 2020
Abstract : OBJECTIVES: Diabetic cystopathy (DC) is recognized as one of the major etiologies of underactive bladder (UAB)/detrusor underactivity (DU). Although DC was first reported about three decades ago, there is a distinct lack of effective pharmacological management methods for UAB/DU due to DC with a robust certainty of evidence. In this study, we investigated whether EP2 and EP3 receptors are promising targets of pharmacological management of UAB/DU due to DC. METHODS: We used streptozotocin (STZ)-induced diabetic Sprague-Dawley rats with postvoid residual urine (PVR) greater than 0.1 mL. Sixteen weeks after induction of diabetes, we performed awake single cystometry after oral administration of the vehicle, an alpha-blocker (tamsulosin [TAM], 0.1 and 0.3 mg/kg), a cholinesterase inhibitor (distigmine [DIS], 0.3 and 1.0 mg/kg), or an EP2/3 dual agonist (ONO-8055, 0.01 and 0.03 mg/kg). We compared cystometric parameters after administration of the vehicle and drugs using a paired t test. P < .05 was considered to be statistically significant. RESULTS: Compared with the vehicle, TAM significantly decreased maximum intravesical pressure during voiding (Pmax), while DIS significantly increased it. However, neither drug significantly affected PVR or the residual urine rate (RUR). On the other hand, ONO-8055 significantly decreased PVR and tended to decrease RUR, although it did not significantly affect Pmax. CONCLUSION: The present study was unable to demonstrate that stimulation of EP2 and EP3 receptors caused major improvements in UAB/DU due to DC. However, this equivocal result could arise from inherent limitations of the STZ-induced diabetic rat as a UAB/DU model.
ESTHER : Sekido_2020_Low.Urin.Tract.Symptoms__
PubMedSearch : Sekido_2020_Low.Urin.Tract.Symptoms__
PubMedID: 32410343

Title : Much caution does no harm! Organophosphate poisoning often causes pancreatitis - Yoshida_2015_J.Intensive.Care_3_21
Author(s) : Yoshida S , Okada H , Nakano S , Shirai K , Yuhara T , Kojima H , Doi T , Kato H , Suzuki K , Morishita K , Murakami E , Ushikoshi H , Toyoda I , Ogura S
Ref : J Intensive Care , 3 :21 , 2015
Abstract : Organophosphate poisoning (OP) results in various poisoning symptoms due to its strong inhibitory effect on cholinesterase. One of the occasional complications of OP is pancreatitis. A 62-year-old woman drank alcohol and went home at midnight. After she quarreled with her husband and drank 100 ml of malathion, a parasympathomimetic organophosphate that binds irreversibly to cholinesterase, she was transported to our hospital in an ambulance. On admission, activated charcoal, magnesium citrate, and pralidoxime methiodide (PAM) were used for decontamination after gastric lavage. Abdominal computed tomography detected edema of the small intestine and colon with doubtful bowel ischemia, and acute pancreatitis was suspected. Arterial blood gas analysis revealed severe lactic acidosis. The Ranson score was 6 and the APACHE II (Acute Physiology and Chronic Health Evaluation) score was 14. Based on these findings, severe acute pancreatitis was diagnosed. One day after admission, hemodiafiltration (HDF) was started for the treatment of acute pancreatitis. On the third hospital day, OP symptoms were exacerbated, with muscarinic manifestations including bradycardia and hypersalivation and decreased plasma cholinesterase activity. Atropine was given and the symptoms improved. The patient's general condition including hemodynamic status improved. Pancreatitis was attenuated by 5 days of HDF. Ultimately, it took 14 days for acute pancreatitis to improve, and the patient discharged on hospital day 32. Generally, acute pancreatitis associated with OP is mild. In fact, one previous report showed that the influence of organophosphates on the pancreas disappears in approximately 72 hours, and complicated acute pancreatitis often improves in 4-5 days. However, it was necessary to treat pancreatitis for more than 2 weeks in this case. Therefore, organophosphate-associated pancreatitis due to malathion is more severe. Although OP sometime causes severe necrotic pancreatitis or pancreatic pseudocysts, it was thought that the present patient had a good clinical course without these complications due to the appropriate intensive care including nafamostat, antibiotics, fluid resuscitation, and HDF. In conclusion, OP-associated pancreatitis requires careful assessment because it may be aggravated, as in this case.
ESTHER : Yoshida_2015_J.Intensive.Care_3_21
PubMedSearch : Yoshida_2015_J.Intensive.Care_3_21
PubMedID: 25949814

Title : Effects of alpha1 Antagonist and Cholinesterase Inhibitor on Cystometric Parameters in Lumbar Canal Stenosis Rats With Underactive Bladder - Sekido_2014_Urology_84_1248 e9
Author(s) : Sekido N , Kida J , Wakamatsu D , Okada H , Matsuya H
Ref : Urology , 84 :1248 e9 , 2014
Abstract : OBJECTIVE: To examine the lower urinary tract function of a rat lumbar canal stenosis (LCS) model by in vivo cystometry before and after alpha1 adrenoceptor antagonist or cholinesterase inhibitor administration. MATERIALS AND
METHODS: One small hole was drilled at the fifth lumbar vertebral arch, and a rectangular piece of silicone rubber was inserted into the L5-L6 epidural space. Two weeks after the surgery, awake cystometry was performed before and after the oral administration of the vehicle, tamsulosin (TAM, 0.03 and 0.1 mg/kg), or distigmine (DIS, 0.3 and 1 mg/kg). We compared the awake cystometry parameters before and after drug administration.
RESULTS: The LCS rats showed a large maximum cystometric capacity (MCC) and a high residual urine rate with a lower maximum bladder pressure during micturition (Pmax). TAM and DIS significantly decreased the pressure at the onset of voiding contraction, MCC, and postvoid residual urine volume. Residual urine rate was also significantly decreased by DIS at 0.3 and 1.0 mg/kg, and TAM at 0.03 mg/kg. DIS significantly increased the frequency of nonvoiding contractions per minute. Pmax was not significantly different even after administration of DIS. CONCLUSION: The LCS rats had salient characteristics of severe infra-sacral neuropathic bladder dysfunction. TAM and DIS decreased postvoid residual urine volume, but this decrease was not accompanied by an increased Pmax or increased voided volume. Rather, decreased MCC was a possible contributing factor. Moreover, increased nonvoiding contractions after administration of DIS might participate in the decreased MCC. This novel model will be useful in studying the pharmacotherapy of the underactive bladder.
ESTHER : Sekido_2014_Urology_84_1248 e9
PubMedSearch : Sekido_2014_Urology_84_1248 e9
PubMedID: 25443946

Title : Effects of ovarian hormone treatment on the gene expression of muscarinic acetylcholine receptors in the ovariectomized rat myometrium - Yasuda_2014_J.Steroid.Biochem.Mol.Biol_143C_81
Author(s) : Yasuda K , Sumi G , Kanamori C , Nakajima T , Tsuzuki T , Cho H , Nishigaki A , Okada H , Kanzaki H
Ref : J Steroid Biochem Mol Biol , 143C :81 , 2014
Abstract : We investigate the effects of ovarian hormone on the gene expression of muscarinic acetylcholine receptors (M1-M5) in the myometrium using real-time PCR and evaluate the relationships between their expression and that of ovarian hormone receptors (ERalpha, ERbeta, and PgR). Wistar rats were sham operated (SO) or ovariectomized (OVX) and treated with vehicle, estradiol (E2), progesterone (P4), or both E2 and P4 for 2 days beginning on postoperative day 33. M1 and M4 mRNA expressions were not detected in the myometrium. M2 mRNA expression did not change significantly in the OVX and OVX+P4 groups compared to the SO group, but increased significantly in the OVX+E2 group and was normalized in the OVX+E2P4 group. M3 mRNA expression increased significantly in the OVX and OVX+P4 groups compared to the SO group, but was normalized in the OVX+E2 and OVX+E2P4 groups. M5 mRNA expression did not change significantly in all experimental groups. ERalpha mRNA expression increased significantly in the OVX, OVX+E2, and OVX+P4 groups compared to the SO group, but was normalized in the OVX+E2P4 group. The changes in ERbeta mRNA expression were similar to those of M3 mRNA expression in all experimental groups. In contrast, the changes in PgR mRNA expression did not correspond with that of M2, M3, or M5 mRNA expression in any of the experimental groups. Additionally, we evaluated the relationship between the expression of muscarinic acetylcholine receptors and ovarian hormone receptors in estrus cycle. M2 mRNA expression increased significantly in diestus and metaestrus compared in proestrus and estrus. M3 mRNA expression increased significantly in only diestrus compared in the other stages. In contrast, M5 mRNA expression did not change in estrus cycle. The changes in ERalpha mRNA expression appeared to be similar to those of M2 in estrus cycle, but no significant difference was found. The changes in ERbeta mRNA expression were similar to those of M3 mRNA expression. The change in PgR mRNA expression increased significantly in diestrus compared in metaestrus, but did not correspond with that of M2, M3, or M5 mRNA expression in estrus cycle. When acetylcholine sensitivity in the myometrium was compared between diestrus and estrus, the sensitivity is significantly lower in estrus than in diestrus. These results suggest that ovarian hormones influence the expression of M2 and M3 in the myometrium by regulating the expression of hormone receptors. E2 may upregulate M2 via ERalpha, but P4 may downregulate M2 by inhibiting ERalpha via PgR. E2 may downregulate M3 by inhibiting ERbeta, but P4 may not regulate the expression of M3 and ERbeta. M5 may be a constitutive muscarinic receptor in the myometrium because neither E2 nor P4 influence the expression of M5. The combination of E2 and P4 may contribute the reproduction by quieting down the acetylcholine-induced myometrial contraction.
ESTHER : Yasuda_2014_J.Steroid.Biochem.Mol.Biol_143C_81
PubMedSearch : Yasuda_2014_J.Steroid.Biochem.Mol.Biol_143C_81
PubMedID: 24583025

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 : 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 : The gene encoding dipeptidyl aminopeptidase BI from Pseudomonas sp. WO24: cloning, sequencing and expression in Escherichia coli - Ogasawara_1998_Gene_206_229
Author(s) : Ogasawara W , Kobayashi G , Ishimaru S , Okada H , Morikawa Y
Ref : Gene , 206 :229 , 1998
Abstract : We have isolated the dipeptidyl aminopeptidase BI (DAP BI) gene from the plasmid library of Pseudomonas sp. WO24 chromosomal DNA by the enzymatic plate assay using a chromogenic substrate. The DAP BI gene, designated dap b1, was further subcloned and sequenced. Sequence analysis of an approx. 3-kb fragment revealed an open reading frame of 2169 nucleotides, which was assigned to the dap b1 gene by N-terminal and internal amino acid sequences. The predicted amino acid sequence of DAP BI containing a serine protease Gly-X-Ser-X-Gly consensus motif displays extensive homologies to the several proteases belonging to the prolyl oligopeptidase family, a novel serine protease family possessing the catalytic triad with a specific array of Ser, Asp and His in this order, which is the hallmark of the member of this family including DAP IV. The dap b1 gene was expressed in Escherichia coli and the expressed enzyme was purified about 230-fold with 2.6% recovery from the cell-free extracts. The enzymatic properties such as molecular mass, substrate specificity and effect of inhibitor were similar to the native enzyme from Pseudomonas sp. WO24.
ESTHER : Ogasawara_1998_Gene_206_229
PubMedSearch : Ogasawara_1998_Gene_206_229
PubMedID: 9469937
Gene_locus related to this paper: psesp-DAP

Title : Two types of novel dipeptidyl aminopeptidases from Pseudomonas sp. strain WO24 - Ogasawara_1996_J.Bacteriol_178_6288
Author(s) : Ogasawara W , Kobayashi G , Okada H , Morikawa Y
Ref : Journal of Bacteriology , 178 :6288 , 1996
Abstract : Two kinds of dipeptidyl aminopeptidase I (DAP I [cathepsin C])-like activities which hydrolyze Gly-Phe-p-nitroanilide (Gly-Phe-pNA) were detected in Pseudomonas sp. strain WO24. They were purified and characterized. The isolated enzymes, named DAP BII and DAP BIII, were revealed to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing. DAP BII was estimated to have a molecular mass of 150,000 Da by gel filtration and a subunit size of 73,000 Da by SDS-PAGE, indicating it to be a homodimer. The molecular mass of DAP BIII was evaluated to be approximately 60,000 Da by gel filtration and 69,000 Da by SDS-PAGE, indicating that it is monomeric. The isoelectric points of DAP BII and DAP BIII were 6.1 and 5.0, and their optimal pHs were 8.0 and 8.5 to 9.0, respectively. The result of peptide mapping for DAP BII and DAP BIII showed that these enzymes consist of different components. Both enzymes were completely inhibited by diisopropylphosphofluoride but not by general thiol inhibitors, indicating that they are serine proteases. DAP BII and DAP BIII hydrolyzed Gly-Phe-pNA but not Gly-Arg-pNA, both of which are model substrates for mammalian DAP I. Despite these shared activities toward DAP I, DAP BII released dipeptides from Ala-Ala-pNA and Lys-Ala-4-methylcoumarinamide (a substrate for DAP II), whereas DAP BIII did not hydrolyze either of these compounds and was presumed to prefer substrates composed of bulky, hydrophobic amino acids at P1 and P1' positions. In addition, DAP BII showed no endopeptidase activity, whereas DAP BIII possessed the activity on N-terminally blocked peptide derivatives besides exopeptidase activity. Assays performed with bioactive peptides such as angiotensin I and neuromedin N as substrates indicate that DAP BII has a considerably broader substrate specificity than DAP BIII and is able to hydrolyze an X-Pro bond, an imido bond that few peptidases and no known DAPs can cleave. These characteristics, namely, substrate specificities, molecular mass, pI, peptide mapping, pH optimum, and effect of inhibitors, suggested that the two DAPs purified in this work are distinct enzymes and do not belong to any of the previously reported DAP classes.
ESTHER : Ogasawara_1996_J.Bacteriol_178_6288
PubMedSearch : Ogasawara_1996_J.Bacteriol_178_6288
PubMedID: 8892831
Gene_locus related to this paper: psemx-dapb3

Title : [The histochemical study of the effects of estrogen on the forebrain cholinergic neurons of fetal female rats transplanted into the anterior eye chamber of adult female rats]. [Japanese] - Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
Author(s) : Tanaka K , Tamura T , Kawashima M , Ueda S , Matsumoto Y , Kawata M , Ogino Y , Yamamoto T , Honjo H , Okada H
Ref : Nippon Naibunpi Gakkai Zasshi Folia Endocrinologica Japonica , 69 :534 , 1993
Abstract : In order to clarify the effects of estrogen on cholinergic basal forebrain neurons, a cholinergic neuron in the diagonal band nucleus of the female fetal rat was implanted into the anterior eye chamber of the female adult rat. Some host rats were treated with 2mg estradiol valerate (E2v) injected every 3 days after ovariectomy while others were not 2 and 4 weeks after transplantation, the growth of cholinergic neurons in the graft was studied using acethylcholinesterase (AChE) histochemistry. At 2 weeks after transplantation, AChE positive neurons and fibers were densely distributed in the grafts of E2v treated rats. Also in grafts without E2v treatment, AChE positive neurons and fibers were found in all the grafts although their density was low. At 4 weeks, AChE staining was dense staining observed in both groups. These results indicate that neurotrophic effect of estrogen on the cholinergic basal forebrain neurons.
ESTHER : Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
PubMedSearch : Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
PubMedID: 8330655