Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
34 巻 , 4 号
選択された号の論文の25件中1~25を表示しています
Review
  • Hideki Hayashi
    原稿種別: Review
    2011 年 34 巻 4 号 p. 453-461
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Lipoproteins in the central nervous system (CNS) are not incorporated from the blood but are formed mainly by glial cells within the CNS. In addition, cholesterol in the CNS is synthesized endogenously because the blood–brain barrier segregates the CNS from the peripheral circulation. Apolipoprotein (apo) E is a major apo in the CNS. In normal condition, apo E is secreted from glia, mainly from astrocytes, and forms cholesterol-rich lipoproteins by ATP-binding cassette transporters. Subsequently, apo E-containing glial lipoproteins supply cholesterol and other components to neurons via a receptor-mediated process. Recent findings demonstrated that receptors of the low density lipoprotein (LDL) receptor family not only internalize lipoproteins into the cells but also, like signaling receptors, transduce signals upon binding the ligands. In this review, the regulation of lipid homeostasis will be discussed as well as roles of lipoproteins and functions of receptors of LDL receptor family in the CNS. Furthermore, the relation between lipid metabolism and Alzheimer's disease (AD) is discussed.
Analytical Biochemistry
Note
  • Satoshi Muto, Yuichi Kouyama, Yuusaku Yokoyama, Hiroaki Okuno, Toshihi ...
    原稿種別: Note
    専門分野: Analytical Biochemistry
    2011 年 34 巻 4 号 p. 562-566
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Taxanes, which are widely used in treatment of numerous cancer types, are well-known to induce hypersensitivity reactions (HSR), especially in the case of paclitaxel. Although the cause of the HSR is commonly thought to be a non-immunological direct effect of the diluent which is used to dissolve paclitaxel, some reports suggest the possibility of the presence of an immunological reaction to the common taxane structure. The aim of this study was to establish a method to determine the presence of anti-taxane antibodies in body fluids of patients who have previously received paclitaxel, in order to estimate the risk of the occurrence of HSR to other taxane compounds, such as docetaxel. To prepare an enzyme-linked immunosorbent assay (ELISA) plate for determining taxanes, 10-deacetylbaccatin III (DAB) was first succinylated by use of dimethylaminopyridine and succinic anhydride in dried pyridine. After the succinylation reaction, three different products were obtained, and these were confirmed as 7-succinoyl DAB (7-DAB), 10-succinoyl DAB (10-DAB), and 7,10-disuccinoyl DAB (7,10-DAB) by 1H-NMR analysis. Each of these three products was conjugated with bovine serum albumin (BSA), and adsorbed on an ELISA plate. By using a commercially available anti-taxane monoclonal antibody as a model antibody, the detection limit of the anti-taxane antibodies on the 7-DAB-BSA-, 10-DAB-BSA-, and 7,10-DAB-BSA-conjugated ELISA plate was estimated as 0.3, 1 and 10 ng/ml, respectively. The ELISA system established in this study may therefore be useful for estimating the risk of HSR to taxanes in a patient prior to the use of these drugs.
Biochemistry
Regular Articles
  • Eisaku Yamamoto, Naoko Nishimura, Ken Okada, Chikako Sekido, Shingo Ya ...
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 4 号 p. 462-470
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Plasma hyaluronan-binding protein (PHBP), a serine protease that can activate coagulation factor VII and prourokinase, circulates in a single-chain form (pro-PHBP) and autoproteolytically converts to an active two-chain form with the aid of an effector such as spermidine and heparin. It has been postulated that PHBP plays roles in regulating inflammation, vascular function, fibrosis and atherosclerosis. From the comprehensive screening of natural sources for inhibitors of spermidine-induced pro-PHBP autoactivation, we identified several compounds with a polyphenol feature. Of these inhibitors, tannic acid (IC50=0.020 μM), delphinidin (IC50=0.079 μM), hamamelitannin (IC50=0.19 μM), (−)-epicatechin gallate (IC50=0.24 μM), and 3,5-di-O-caffeoylquinic acid (IC50=1.0 μM) were potent and selective, and did not inhibit heparin-induced pro-PHBP autoactivation and the active form of PHBP at concentrations 100 times higher than the respective IC50 values. From evaluation of the activities of related compounds, it has been suggested that a compound with multiple aromatic rings with plural phenolic hydroxyl substituents exhibits potent activity. The inhibitory actions of delphinidin, hamamelitannin, (−)-epicatechin gallate and 3,5-di-O-caffeoylquinic acid were attenuated by catechol, a minimum polyphenol unit. Thus, it is likely that pro-PHBP binds these potent inhibitors through its site(s) that recognize a catechol-like structure. Our results would facilitate understanding of the molecular mechanism of pro-PHBP autoactivation and rational design of a compound for suppressing unregulated pro-PHBP activation.
  • Alena Rajnochová Svobodová, Adéla Galandák ...
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 4 号 p. 471-479
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    The ultraviolet (UV) region of solar radiation is a critical factor in the initiation and development of a number of skin diseases. However, it is not only skin which is directly exposed to solar light that is affected by UV radiation, through low molecular weight mediators, generated upon irradiation, “non-skin” tissues can also be affected. The aim of this study was to examine in detail, the acute effects of UVA and UVB wavebands on hairless mice. Female SKH-1 hairless mice were exposed to a single dose of UVB (200, 800 mJ/cm2) or UVA (10, 20 J/cm2) using a solar simulator. The effects on haematological parameters, activity and/or expression of antioxidant enzymes, level of glutathione (GSH), markers of oxidative damage (lipid peroxidation and carbonylated proteins) were analysed in erythrocytes, plasma, liver and whole skin homogenates. No macroscopic changes were observed either 4 or 24 h after UVA/UVB exposure. The blood count showed a significant increase in leukocyte number and reduction of platelets 4 h following UVA and UVB irradiation, which disappeared 24 h after irradiation except for the higher UVA dose. Changes in oxidative stress-related parameters, particularly activity of catalase (CAT) and superoxide dismutase (SOD) and level of GSH and lipid peroxidation products, were found in skin, erythrocytes and liver. The expression of several enzymes (CAT, SOD, glutathione transferase (GST), nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (NQO1) and hem oxygenase-1 (HO-1)) in skin was affected following UVA and UVB radiation. Increase in carbonylated proteins was found in plasma and skin samples.
  • Xin Xin, Koji Higai, Yuzo Imaizumi, Chiho Suzuki, Kenichiro Ito, Ayumi ...
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 4 号 p. 480-485
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Killer lectin-like receptors on natural killer (NK) cells mediate cytotoxicity through glycans on target cells. We prepared recombinant glutathione S-transferase-fused extracellular lectin-like domains (AA 94-231) of natural killer group 2A (NKG2A) (rGST-NKG2A) and NKG2C (rGST-NKG2C) and determined the binding of these receptors to plates coated with heparin-conjugated bovine serum albumin (heparin-BSA) and glycoproteins. rGST-NKG2A and rGST-NKG2C directly bound to heparin-BSA with Kd values of 20 and 40 nM, respectively. Binding of rGST-NKG2A and rGST-NKG2C to heparin-BSA was suppressed in the presence of soluble heparin, heparan sulfate, fucoidan, λ-carrageenan, and dextran sulfate. 2-O-Sulfate residues in heparin were essential for the binding of rGST-NKG2A and rGST-NKG2C. Moreover, rGST-NKG2A and rGST-NKG2C bound to multimeric sialyl Lewis X expressing transferrin secreted by HepG2 cells with Kd values of 80 and 114 nM, respectively. This is the first report showing that NKG2A and NKG2C bind to heparin and α2,3-NeuAc-containing glycoproteins.
Note
Molecular and Cell Biology
Regular Articles
  • Seong-Min Kwon, Soo-A Kim, Shinsuke Fujii, Hidefumi Maeda, Sang-Gun Ah ...
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 4 号 p. 486-489
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Transforming growth factor β1 (TGF-β1) regulates cellular functions including cell growth, differentiation, and migration. However, signal transduction pathways of TGF-β1 are mostly undefined in human periodontal ligament (hPDL) cells. In this study, we investigated TGF β1-induced migration focusing on heat shock protein 27 (Hsp27) activation. The cellular response to TGF-β1 by hPDL cells was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis. Cell migration was determined by counting migrated cells using a Chemotaxis Cell Migration Assay kit. TGF-β1 induced cell migration and increased the phosphorylation of Hsp27 and p38 mitogen-activated protein kinase (MAPK) in hPDL cells. Inhibiting p38 MAPK with SB203580 blocked TGF-β1-induced Hsp27 activation and cell migration. These findings suggest that TGF-β1-induced Hsp27 may promote the migration of hPDL cells via p38 MAPK mediated signaling. Hsp27 may be a potential target for the periodontal regeneration process related to cell migration.
  • Sachiko Juman, Naomi Yasui, Hiroto Okuda, Ai Ueda, Hiroko Negishi, Tom ...
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 4 号 p. 490-494
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    We previously reported that caffeic acid phenethyl ester (CAPE) suppresses 3T3-L1 differentiation to adipocytes through the inhibition of peroxisome proliferator-activated receptor (PPAR) gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, fatty acid synthase (Fas) and adipocytes-specific fatty acid binding protein 2 (aP2) expressions (Juman et al., Biol. Pharm. Bull., 33, 1484—1488 (2010)). In the present study, we confirmed that CAPE had inhibitory effects on increased glycerol-3-phosphate dehydrogenase (GPDH) activity and an increased insulin receptor substrate 1 (IRS-1). Our data show that treatment with 50 μM CAPE significantly reduced the levels of leptin (p<0.05), resistin (p<0.05) and tumor necrosis factor (TNF)-alpha (p<0.05) which are known to aid adipocytokines production in adipocytes. In 3T3-L1 cells, treatment of CAPE decreased the triglyceride deposition similar to resveratrol, which is known to have an inhibitory effect on 3T3-L1 differentiation to adipocytes. In conclusion, we found that CAPE suppresses the production and secretion of adipocytokines from mature adipocytes in 3T3-L1 cells.
  • Jin Chung, Young-Ok Yoon, Jun Sik Lee, Tae Kwun Ha, Sung Mock Ryu, Kwa ...
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 4 号 p. 495-500
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Dendritic cells are professional antigen-presenting cells that are responsible for initiating of the immune response. However, there are no reports on how the polysaccharides in an oral biofilm affect the viability of dendritic cells. Inulin, a fructooligossacharide, is one component of oral biofilm fructan that is used as an energy source by oral bacteria. In this study, we found that murine bone marrow derived dendritic cells were induced to undergo apoptosis after being treated with inulin in a dose-dependent manner, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), annexinV/propidium iodide (PI), and Hoechest staining methods. Inulin activated the apoptotic pathway, including caspase-9 and caspase-3, decreased the level of B-cell lymphoma 2 (Bcl-2) expression, increased the expression of the Bcl-2-associated X protein (Bax) protein and induced poly(ADP-ribose) polymerase (PARP) cleavage. These observations suggest that inulin induces the apoptosis of dendritic cells by altering the Bcl-2/Bax ratio through the caspase dependant pathway. These results indicated that high concentrations of inulin can cause apoptic cell death in murine bone marrow-derived dendritic cells.
  • Kyohei Oyama, Kiyoshi Takahashi, Koichi Sakurai
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 4 号 p. 501-506
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Cell cycle arrest is associated with differentiation, senescence and apoptosis. We investigated alterations in the cell cycle during the development of hypertrophy induced by hydrogen peroxide (H2O2) in the H9c2 clonal myoblastic cell line. H2O2 induced hypertrophy in H9c2 cells that was indicated by an increase in atrial natriuretic peptide (ANP) gene expression, a marker of cardiomyocyte hypertrophy, and a larger cell size. On induction of hypertrophy by H2O2 in H9c2 cells, cell proliferation was arrested, indicated by the number of cells remaining constant during a 72-h incubation period. The cell cycle was arrested at the G1 and G2/M phases with an increase in p21 expression, a negative cell cycle regulator. Cell cycle arrest and increase in p21 expression were significantly inhibited by 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM), an intracellular calcium chelator. Although ANP gene expression was induced significantly, H2O2 failed to induce hypertrophy in the presence of BAPTA-AM, and the cell cycle progressed. We concluded that H2O2 induced cell cycle arrest in H9c2 cells, which was related to cellular hypertrophy.
Microbiology
Note
  • Tomotaka Tanabe, Tatsuya Funahashi, Katsushiro Miyamoto, Hiroshi Tsuji ...
    原稿種別: Note
    専門分野: Microbiology
    2011 年 34 巻 4 号 p. 570-574
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    We found that Vibrio (V.) furnissii ATCC35016 can gain iron through a xenosiderophore desferrioxamine B (DFOB) for its growth under iron-limiting conditions, concurrent with the expression of the 79-kDa iron-repressible outer membrane protein (IROMP) in response to the presence of DFOB. Based on the sequence of the ferrioxamine B (an iron-bound form of DFOB) receptor gene in V. vulnificus, two V. furnissii genes, termed desA and desR, encoding the 79-kDa IROMP and AraC-type transcriptional regulator, respectively, were identified and cloned. Nucleotide sequences located in the promoter regions of both desR and desA predicted the presence of consensus ferric uptake regulation (Fur)-binding sequences. The transcription of both genes was negatively regulated by exogenous iron levels. Deletion of the desA gene abolished the ability of V. furnissii to utilize DFOB, and neither desA mRNA nor DesA was detected in the deletion mutant of desR regardless of the presence of DFOB. The functions of DesA and DesR as the ferrioxamine B receptor and transcriptional activator for desA, respectively, were confirmed by complementation of desA and desR deletion mutants.
Pharmacology
Regular Articles
  • Yuh Suzuki, Toshio Inoue, Atsuki Yamamoto, Yukio Sugimoto
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 507-510
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    The prophylactic use of anti-allergic drugs has been proposed to be effective in the treatment of seasonal allergic rhinitis in humans. However, there is little information regarding the prophylactic effect of thromboxane A2 (TXA2) receptor antagonist on allergic rhinitis. Recent studies revealed that a TXA2 receptor antagonist ramatroban could block the prostaglandin D2 (PGD2) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). In the present study, we investigated the prophylactic effects of the histamine H1 receptor antagonist epinastine and the TXA2 receptor antagonist ramatroban and seratrodast on mouse models of allergic rhinitis. Female BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin and alum on days 0, 5, 14 and 21. Seven days later, mice were sensitized by intranasal application of ovalbumin thrice a week. Drugs were administered once a day from day 22. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms (sneezing and nasal rubbing). Histamine sensitivity and eosinophil infiltration into the nasal mucosa were also determined. Epinastine and ramatroban significantly reduced nasal symptoms and the number of eosinophils in the nasal mucosa. Seratrodast showed no effect on nasal symptoms and eosinophil infiltration into the nasal mucosa. In addition, histamine sensitivity was reduced by epinastine and ramatroban. These results indicate that epinastine and ramatroban induce the prophylactic effect on allergic rhinitis.
  • Lin Wang, Ming Jin, Bao-Xia Zang, Yan Wu
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 511-516
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Myofibroblast plays an important role in the progression of pulmonary fibrosis, featured by the presence of α-smooth muscle actin (α-SMA). It has been a novel therapeutic target. Safflor yellow (SY) is extracted from safflower, a traditional Chinese medicine. The aim of our study is to investigate the effects of SY on rats of pulmonary fibrosis induced by bleomycin (BLM) and on differentiation of lung fibroblast into myofibroblast stimulated by transforming growth factor-β1 (TGF-β1). Two dose SY (intraperitoneal, 25, 50 mg/kg/d) were administered to rats treated by BLM consecutively for four weeks. It was found that SY alleviated the loss in body weight, the increase of hydroxyproline content in the lung tissues and pathologic changes of pulmonary fibrosis caused by BLM instillation. SY also prevented the increase of α-SMA positive cells and TGF-β1 expression induced by BLM. These effects were more significant when treatment with high-dose SY. Moreover, SY (0.05, 0.25, 1.25 mg/ml) inhibited the expression of α-SMA during differentiation of lung fibroblast into myofibroblast stimulated by TGF-β1. SY had anti-fibrotic effect in experiment and might be employed as a therapeutic candidate agent for attenuating pulmonary fibrosis.
  • Yan He, Fen Liu, Lurong Zhang, Yan Wu, Bo Hu, Yinsheng Zhang, Yunsen L ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 517-522
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Hepatocellular carcinoma (HCC) is the fifth most malignant tumor worldwide and is known to be resistant to conventional chemotherapy. New therapeutic strategies are urgently needed for treating HCC. Lup-20(29)-en-3H-ol (Lupeol), a novel dietary triterpene, is found in fruits, vegetables, and medicinal plants and possesses multiple bio-activities with very low toxicity. In the current study, we investigated its growth-inhibitory effects in HCC cell lines SMMC7721 and HepG2. In the in vitro studies, lupeol treatment alone caused decrease of cell viability in two HCC cell lines in a dose-dependent manner. It also induced apoptosis and caused cell accumulation in S phase. Further analysis revealed the induction of active caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage by lupeol treatment. In the in vivo studies, nude mice implanted with SMMC7721 cells subcutaneously were treated with lupeol three times a week and tumor development was significantly inhibited. We further investigated the combination anti-tumor effect of lupeol and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HCC, considering TRAIL treatment alone could not achieve high level of anti-tumor effect. The results demonstrated that lupeol could exert a combinational effect with TRAIL, resulting in chemosensitization of HCC. Our results suggested that lupeol alone or as an adjuvant to therapeutic agents could be developed as a potential agent for treating HCC.
  • Byung-Hwan Lee, Sung-Hee Hwang, Sun-Hye Choi, Tae-Joon Shin, Jiyeon Ka ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 523-527
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Resveratrol, which is found in grapes, red wine, and berries, has many beneficial health effects, such as anti-cancer, neuro-protective, anti-inflammatory, and life-prolonging effects. However, the cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. 5-Hydroxytryptamine type 3A (5-HT3A) receptor is one of several ligand-gated ion channels involved in fast synaptic transmission. In the present study, we investigated the effect of resveratrol on mouse 5-HT3A receptor channel activity. 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured using a two-electrode voltage clamp technique. Treatment of resveratrol itself had no effect on the oocytes injected with H2O as well as on the oocytes injected with 5-HT3A receptor cRNA. In the oocytes injected with 5-HT3A receptor cRNA, co- or pre-treatment of resveratrol with 5-HT potentiated 5-HT-induced inward peak current (I5-HT) with concentration-, reversible, and voltage-independent manners. The EC50 of resveratrol was 28.0±2.4 μM. The presence of resveratrol caused a leftward shift of 5-HT concentration–response curve. Protein kinase C (PKC) activator or inhibitor had no effect on resveratrol action on I5-HT. Site-directed mutations of pre-transmembrane domain 1 (pre-TM1) such as R222A, R222D, R222E, R222K, and R222T abolished or attenuated resveratrol-induced enhancement of I5-HT, indicating that resveratrol might interact with pre-TM1 of 5-HT3A receptor. These results indicate that resveratrol might regulate 5-HT3A receptor channel activity via interaction with the N-terminal domain and these results further show that resveratrol-mediated regulation of 5-HT3A receptor channel activity might be one of cellular mechanisms of resveratrol action.
  • Takaharu Ishibashi, Naoki Nishizawa, Mihoko Nakamoto-Nomura, Fusae Abe ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 528-537
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    A possible cause of arterio-venous (A-V) differences in plasma nitrite (NO2) levels under steady-state conditions and kinetic features of NO2 in arterial and venous blood were examined. In isolated rabbit blood, plasma NO2 in venous blood disappeared faster than that in arterial blood and was accompanied by a concomitant increase in nitrate (NO3), implicating oxidation as the main pertinent metabolic pathway. When data were corrected with respective elimination constants and time durations before plasma separation, no A-V difference was estimated under steady-state. Even after these corrections for NO2 loading in anesthetized rabbits, a large A-V difference in NO2 levels (arterial venous) was observed, followed by an exponential decrease in NO2 levels without a reciprocal increase in NO3 levels. There was a marked difference in NO2 decay between in vivo and ex vivo experiments, but no increases in the circulating blood were detected for other substances derived from NO2, such as methemoglobin or low- and high-molecular weight nitrosothiols. In rats and guinea pigs, absence and presence of the A-V difference were detected under steady-state conditions and after NO2 loading, respectively. These observations indicate that apparent A-V differences under steady-state are artifacts arising from different rates of NO2 disappearance in arterial versus venous plasma during sample handling, and that tissue compartments may contribute to changes in NO2 levels in circulating blood. Therefore, caution is required when evaluating plasma NO2 levels, especially in venous blood.
Note
  • Min-Ho Jung, Min-Cheol Song, Kiho Bae, Han Sung Kim, Seung Hyun Kim, S ...
    原稿種別: Note
    専門分野: Pharmacology
    2011 年 34 巻 4 号 p. 575-579
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    We investigated the effects of sauchinone, isolated from the root of Saururus chinensis, on muscle disorders and the underlying mechanism of oxidative stress-induced C2C12 skeletal muscle myoblast damage. To assess the protective effects of sauchinone on oxidative stress-induced C2C12 skeletal muscle myoblasts, we measured the viability of the cells, showing that sauchinone pre-treatment significantly reduced the decreased cell viability after H2O2 treatment. We also investigated the mechanism of this protective effect of sauchinone. In Western blot analysis, the heat shock protein (HSP)-70 level increased significantly in the sauchinone-pretreated myoblasts. We used high performance liquid chromatography (HPLC) to examine the level of endogenous ceramide after pre-treatment with sauchinone followed by exposure to H2O2. While hydrogen peroxide increased the ceramide content to approximately 166.60±38.93% of the control level, pre-treatment with sauchinone inhibited this increase, maintaining the ceramide content at the control level. We demonstrated that sauchinone regulates intracellular HSP70 expression as well as ceramide levels to protect against oxidative stress-induced C2C12 muscle myoblast damage. We suggest the potential benefits of herbal medicines in the treatment of oxidative stress-related muscle disorders.
Medicinal Chemistry
Regular Article
  • Ju-Young Park, Seung-Woo Kim, Ja-Kyeong Lee, Weon Bin Im, Byung Kwan J ...
    原稿種別: Regular Article
    専門分野: Medicinal Chemistry
    2011 年 34 巻 4 号 p. 538-544
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    A series of fluoxetine, where the N-methylamino group was replaced and then simplified, were synthesized and their inhibitory effect was tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. Although the synthesized compounds generally revealed weaker activity or greater cytotoxicity than fluoxetine, compound 10a, in which the N-methylamino group in fluoxetine was replaced by morpholine, and the trifluoromethylphenyl ring was substituted with simple oxo group, suppressed NO production dose-dependently at 10, 20 and 40 μM concentrations with less cytotoxicity than fluoxetine, and inhibited iNOS mRNA and protein expression at the same concentrations in LPS-induced BV2 cells. The results suggested that the trifluoromethylphenyl ring moiety in fluoxetine is not necessary for the suppression of NO production and that 10a has the potential as a potent inhibitor of NO production.
Pharmacognosy
Note
  • Ji-Hyun Kim, Yeong-In Yang, Kyung-Tae Lee, Hee-Juhn Park, Jung-Hye Cho ...
    原稿種別: Note
    専門分野: Pharmacognosy
    2011 年 34 巻 4 号 p. 580-585
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Endometriosis, a disease affecting 5—15% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Costunolide, a sesquiterpene lactone, has anti-proliferative and pro-apoptotic activities that may be efficacious in therapy for endometriosis. In the present study, we investigated the effect of costunolide on the cell growth and apoptosis of endometriotic cells. We found that costunolide significantly inhibited the cell viability of 11Z and 12Z human endometriotic epithelial cells. Interestingly, endometriotic cells were more sensitive to costunolide treatment than immortalized endometrial cells (HES). Costunolide induced apoptosis of 11Z cells in a time-dependent manner as shown by accumulation of sub-G1 population. In addition, treatment with costunolide induced the activation of caspase-3, -8, and -9 in a dose- and time-dependent manner. Pretreatment with the broad caspase inhibitor z-VAD-fmk significantly reversed the costunolide-induced inhibition of cell viability in 11Z cells. We further demonstrated that costunolide inhibited the activation of Akt and nuclear factor kappa B (NFκB) and the expression of anti-apoptotic factors B-cell lymphoma-extra lage (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) in 11Z cells. These results suggest that costunolide induces apoptosis in human endometriotic epithelial cells by inhibiting the prosurvival NFκB and Akt pathway, leading to the downregulation of anti-apoptotic protein Bcl-xL and XIAP and the activation of caspases.
Biopharmacy
Regular Articles
  • Haining Tan, Guoying Mu, Wei Zhu, Jinfeng Liu, Fengshan Wang
    原稿種別: Regular Article
    専門分野: Biopharmacy
    2011 年 34 巻 4 号 p. 545-550
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    The aim was to study the effects and action mechanism of endostatin (ES), low molecular weight heparin-endostatin (LMWH-ES) and polyethylene glycol-endostatin (PEG-ES) on endothelial cell proliferation, choroidal neovascularization and zebrafish angiogenesis. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro. Choroidal neovascularization model was used to evaluate the effects of ES and its derivatives on choroidal neovascularization in vivo. Western blotting was employed to study the effects of ES and its derivatives on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in chorioid tissues. Zebrafish model was also used to study the anti-angiogenesis activities of ES and its derivatives. The results showed that ES and its derivatives could significantly inhibit endothelial cell proliferation in vitro (p<0.05), suppress choroidal neovascularization by down-regulating expression of VEGF and up-regulating expression of PEDF in chorioid tissues, and restrain angiogenesis in zebrafish. ES showed better activity in inhibiting endothelial cell proliferation in vitro (p<0.05), but LMWH-ES and PEG-ES showed higher activity in inhibiting choroidal neovascularization in vivo (p<0.05) and angiogenesis in zebrafish (p<0.05). These results indicate that LMWH-endostatin and PEG-endostatin are potential candidates for anti-angiogenesis drug.
  • Takuya Umemoto, Tomohiro Asai, Koji Hirashima, Kosuke Shimizu, Motohir ...
    原稿種別: Regular Article
    専門分野: Biopharmacy
    2011 年 34 巻 4 号 p. 551-554
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Transcription-dependent apoptosis triggered by p53 hardly occurs in alternative reading frame (ARF)-null cancer cells. Loss of ARF leads to hyperactivation of murine double minute 2 (MDM2), resulting in the degradation of p53. In the present study, A549 (ARF-null) human non-small lung cancer cells were transfected with a plasmid DNA encoding human wild-type p53 and the mitochondrial transmembrane domain of Tom5 (p53-Tom5) for delivering p53 to mitochondria. As a result, p53-Tom5 exclusively localized at mitochondria in A549 cells and suppressed the proliferation of them, whereas wild-type p53 did not. In addition, mitochondrial dysfunction and release of cytochrome c were induced by p53-Tom5 in A549 cells. These data suggest that p53-Tom5 suppressed the proliferation of A549 cells through direct mitochondrial dysfunction.
  • Hiroyuki Takeuchi, Shuichi Terasaka, Takanobu Sakurai, Atsushi Furuya, ...
    原稿種別: Regular Article
    専門分野: Biopharmacy
    2011 年 34 巻 4 号 p. 555-561
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    The purpose of this study was to evaluate the variations in the in vitro Yucatan micropig (YMP) skin permeabilities of drugs and to clarify whether YMP skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate and flurbiprofen, through YMP skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in YMP skin permeability for the three model drugs were smaller than that in human skin permeability, and the permeation rates of the three model drugs through the YMP skin were approximately half that through human skin. In addition, the intra-individual variations in YMP skin permeability for nicorandil and flurbiprofen were much smaller than the inter-individual variations in YMP skin. The inter- and intra-regional variations in YMP skin permeability were very small. The markedly smaller variation in the permeability through YMP skin as compared with that through human skin indicated that in vitro permeation studies using YMP skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.
Note
  • Kazuhiko Matsuo, Yumiko Ishii, Ying-Shu Quan, Fumio Kamiyama, Yohei Mu ...
    原稿種別: Note
    専門分野: Biopharmacy
    2011 年 34 巻 4 号 p. 586-589
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    The development of a simple, easy-to-use, and noninvasive vaccination system is in high demand. For transcutaneous immunization (TCI), we previously reported that a hydrogel patch was an effective TCI device that accelerates antigen penetration through the stratum corneum in mouse and rat models. The present study was performed to characterize the transcutaneous protein delivery induced by the hydrogel patch in mouse, guinea pig, LWD pig, human, or tissue-engineered skin models, and to assess the activity of proteins delivered into the skin. The hydrogel patch promoted protein penetration through the stratum corneum in all skin models, indicating that our original hydrogel patch might have practical application for use in humans. In addition, proteins delivered into the skin by the hydrogel patch retained their activity, suggesting that the hydrogel patch is applicable for the delivery of therapies for other diseases as well. On the basis of these results, translational research in human is now in progress.
Miscellaneous
Note
  • Kohei Kawakami, Ken-ichi Matsumoto
    原稿種別: Note
    専門分野: Miscellaneous
    2011 年 34 巻 4 号 p. 590-593
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
    Tenascin-X (TNX) is the largest member in the tenascin family of large oligomeric glycoproteins of the extracellular matrix (ECM). TNX is expressed in the leptomeningeal trabecula and connective tissue of choroid plexus in the brain as well as in muscular tissues. Interestingly, single nucleotide polymorphism (SNP) analysis in human showed that TNX is significantly associated with schizophrenia. Previously we generated TNX-deficient (TNX−/−) mice by homologous recombination using embryonic stem (ES) cells. In the present study, we analyzed behaviors relevant to affect, learning and memory, and motor control in TNX−/− mice. TNX−/− mice showed increased anxiety in light–dark and open-field tests and superior memory retention in a passive avoidance test. Also, TNX−/− mice displayed higher sensorimotor coordination than did wild-type mice in a rotorod test. However, TNX−/− mice did not differ from wild-type mice in locomotor activity in a home-cage activity test using telemetric monitoring. These findings suggest that TNX has diverse roles including roles in behavioral functions such as anxiety, emotional learning and memory, and sensorimotor ability.
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