• Title/Summary/Keyword: Akt1

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Evaluation of fish oil-rich in MUFAs for anti-diabetic and anti-inflammation potential in experimental type 2 diabetic rats

  • Keapai, Waranya;Apichai, Sopida;Amornlerdpison, Doungporn;Lailerd, Narissara
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.6
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    • pp.581-593
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    • 2016
  • The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

Endogenous catalase delays high-fat diet-induced liver injury in mice

  • Piao, Lingjuan;Choi, Jiyeon;Kwon, Guideock;Ha, Hunjoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.317-325
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    • 2017
  • Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy

  • Lv, Yongzhu;Li, Bing;Han, Kunna;Xiao, Yang;Yu, Xianjun;Ma, Yong;Jiao, Zhan;Gao, Jianjun
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.6
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    • pp.617-625
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    • 2018
  • Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.

Molecular Mechanism of Macrophage Activation by Exopolysaccharides from Liquid Culture of Lentinus edodes

  • Lee, Ji-Yeon;Kim, Joo-Young;Lee, Yong-Gyu;Rhee, Man-Hee;Hong, Eock-Ki;Cho, Jae-Youl
    • Journal of Microbiology and Biotechnology
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    • v.18 no.2
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    • pp.355-364
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    • 2008
  • Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. ${\beta}$-Glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using exopolysaccharides prepared from liquid culture of Lentinus edodes. We found that fraction II (F-II), with large molecular weight protein polysaccharides, is able to strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production, cytokine expression, and morphological changes. F-II triggered the nuclear translocation of NF-${\kappa}B$ and activated its upstream signaling cascades such as PI3K/Akt and MAPK pathways, as assessed by their phosphorylation levels. The function-blocking antibodies to dectin-1 and TLR-2, but not CR3, markedly suppressed F-II-mediated NO production. Therefore, our data suggest that mushroom-derived ${\beta}$-glucan may exert its immunostimulating potency via activation of multiple signaling pathways.

Anti-inflammatory Effect of an Ethyl Acetate Fraction from Myagropsis yendoi on Lipopolysaccharides-stimulated RAW 264.7 Cells (LPS로 유도된 RAW 264.7 대식세포에 대한 애기외톨개 모자반(Myagropsis yendoi) 에틸아세테이트 분획물의 항염증 효과)

  • Kim, Bowoon;Kim, Jae-Il;Kim, Hyeung-Rak;Byun, Dae-Seok
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.47 no.5
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    • pp.527-536
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    • 2014
  • An ethanolic extract from Myagropsis yendoi was fractionated using several solvents. Among these, an ethyl acetate fraction (Myagropsis yendoi ethyl acetate fraction: MYE) showed the highest anti-inflammatory activity based on inhibition of lipopolysaccharides (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. We thus investigated the molecular mechanisms underlying MYE's inhibitory effects. Pretreatment of cells with up to $30{\mu}g/mL$ of MYE significantly inhibited NO production and inducible nitric oxide synthase expression in a dose-dependent manner (P<0.05). Similarly, MYE markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$, as well as their mRNA levels. While the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) was strongly suppressed by MYE, the activation of a nuclear factor erythroid 2-related factor (Nrf2) was increased. Moreover, MYE significantly reduced the phosphorylation of JNK, p38 MAPK, and phosphatidylinositol 3-kinase/Akt in LPS-stimulated cells. These results indicate that MYE contains anti-inflammatory compounds, and that it might be used as a dietary supplement for the prevention of inflammatory diseases.

Anti-Inflammatory Effect of Ethyl Acetate Fraction Isolated from Undaria pinnatifida on Lipopolysaccharides-Stimulated RAW 264.7 Cells (LPS로 유도된 RAW 264.7 대식세포에 대한 미역(Undaria pinnatifida) Ethyl Acetate 분획물의 항염증 효과)

  • Choi, Min-Woo;Kim, Jae-Il
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.46 no.4
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    • pp.384-392
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    • 2013
  • An ethanolic extract of Undaria pinnatifida was fractionated using several solvents. Of the fractions, the ethyl acetate fraction had the greatest inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells. Using this fraction (U. pinnatifida ethyl acetate extract, UPE), we investigated the molecular mechanism underlying its inhibitory effect on LPS-stimulated RAW 264.7 cells. Pretreatment of the cells with up to $100{\mu}g/mL$ UPE significantly inhibited NO production and inducible nitric oxide synthase (iNOS) expression, in a dose-dependent manner. Similarly, UPE treatment markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), while it strongly suppressed the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) by preventing proteolytic degradation of inhibitor of nuclear factor ${\kappa}B$ $(I{\kappa}B)-{\alpha}$. Moreover, UPE treatment significantly reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated cells. These results indicate that UPE contains anti-inflammatory compounds and suggest that it might be used as a functional food material that assists in prevention of inflammatory diseases.

Experimental Study on the Anti-depressive Effect of Bee Venom Injection (봉독이 우울증 모델 흰쥐에게 미치는 영향)

  • Lee, Jin-Hee;Kim, Geun-Woo;Koo, Byung-Soo
    • Journal of Oriental Neuropsychiatry
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    • v.21 no.2
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    • pp.61-73
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    • 2010
  • Objectives : The purpose of this study was to assess anti-depressive effects of Bee Venom(BV) on an Animal Model of Depression induced immobility stress. Methods : There was 2 pre-experiments MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Western blot test and 3 main experiments ; forced swimming test, tail suspension test and Y-maze task. Male rats were used for main experiment. The subject was divided into 4 groups(1. control group injected only saline, without immobility stress 2. Negative group injected saline after 2 hours immobility stress 3. Positive group injected Amitriptyline after 2 hours immobility stress 4. BV group injected Bee Venom after 2 hours immobility stress). Each group consisted of 6 rats. Forced swimming test, tail suspension test, Y-maze task were used to evaluate anti-depressive effect of Bee Venom. Results : In MTT assay, as the density of BV increased, the existence rate of primary neuronal cell increased. In Western blot test, the density of CREB and AKT was increasing as time went by. In forced swimming test, BV group showed immobility decreased more than Normal group and Positive group. In tail suspension test, Normal group and Positive group showed immobility decreased more than BV group. In Y-maze task, BV group showed immobility decreased more than Normal group, but Positive group showed immobility decreased more than BV group. Conclusions : These results suggest that Bee Venom may have anti-depressive effect on depression.

Improvement of K+ and Na+ Ion homeostasis and salt tolerance by Co-inoculation of arbuscular mycorrhizal fungi (AMF) and spore associated bacteria (SAB)

  • Selvakumar, Gopal;Kim, Kiyoon;Roy, C. Aritra;Jeon, Sunyong;Sa, Tongmin
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.246-246
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    • 2017
  • Salinity inhibits plant growth and restricts the efficiency of arbuscular mycorrhizal fungi. The selective uptake of nutrients from the soil and their effective transport to host roots make it essential for plant growth and development under salt stress. AMF spore associated bacteria shown to improve mycorrhizal efficiency under stress. Thus, this study aimed to understand the co-inoculation efficiency of AMF and SAB on maize growth and ion homeostasis under salt stress. Two AMF strains and one SAB were inoculated with maize either alone or in combination with one another. The results of our study showed that AMF and SAB co-inoculation significantly improved dry weight and nutrient uptake of maize under salt stress. Co-inoculation significantly reduced proline accumulation in shoots and Na+ accumulation in roots. Co-inoculation treatment also exhibited the high K+/Na+ ratios in roots at 25 mM NaCl. Mycorrhizal colonization showed positive influence for regulation of ZmAKT2, ZmSOS1 and ZmSKOR gene expressions, contributing to K+ and Na+ ion homeostasis. CLSM view showed that SAB were able move and localize into inter and intra cellular spaces of maize roots. In addition, CLSM view of AMF spores showed that gfp-tagged SAB also associated on the spore outer hyaline layer.

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Fagopyrum esculentum Extract Suppresses the Release of Inflammatory Mediator and Proximal Signal Events in $Fc{\varepsilon}RI$-mediated RBL-2H3 Cell Activation (교맥(蕎麥)의 비만세포 염증매개물질의 분비와 $Fc{\varepsilon}RI$ 신호전달에 미치는 효과)

  • Kang, Kyung-Hwa
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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    • pp.469-474
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    • 2012
  • Fagopyrum esculentum(FE) is an important food crop and medicinal plant that is used to improve diabetes, obesity, hypertension, hypercholesterolemia and constipation in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. We investigated the effects on the release of inflammatory mediator and proximal signal events in $Fc{\varepsilon}RI$-mediated RBL-2H3 cell activation. FE reduced antigen (DNP-HSA)-induced release of histamine, prostaglandin D2 (PGD2) and cysteinyl Leukotriene (cysLT) in IgE-sensitized RBL-2H3 cells. In addition, it inhibited antigen-induced HDC2 and COX-2 and 5-LO mRNA expression in IgE-sensitized RBL-2H3 cells. FE also suppressed antigen-induced $Fc{\varepsilon}RI{\beta}$ and $Fc{\varepsilon}RI{\gamma}$ subunit mRNA expression in these cells. To identify the mechanisms underpinning the inhibition of release of inflammatory mediators such as histamine and PGD2 and cysLT by FE, we examined the proximal signal events of intracellular FceRI signaling molecules. FE suppressed antigen-induced phosphorylation of Lyn, Syk, LAT, $PLC{\gamma}1$, PI3K, Akt and cPLA2. Collectively, the anti-allergic effects of FE in vitro suggest its possible therapeutic application to inflammatory allergic diseases, in which its inhibition of inflammatory mediator and FceRI-dependent signaling events in mast cells may be hugely beneficial.

Zu Ethos und Pathos in Hitlers Reden (히틀러 연설에서의 에토스와 파토스에 관하여)

  • Kim Tschong-Young
    • Koreanishche Zeitschrift fur Deutsche Sprachwissenschaft
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    • v.10
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    • pp.231-249
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    • 2004
  • In dieser Albeit wird der Versuch unternommen, die Charakteristik der Rhetorik von Hitler zu analysieren. Im Abschnitt fwei wird die allgemeine Charakteristik der Hillers Reden beschrieben. Die Reden von Hitler sind Elemente eines verzweigten, flexiblen und inhaltlich nor schwer bestimmten Komplexes von Manipulations-und Machttechniken, die trotz seiner Tendenz zur Zentralisierung nur schwer als System zu fassen sind. Dies macht die Schwierigkeit jeder analytischen Erfassung aus. Seine Rede vermag im Bezug auf Logik und Argumentation wenig zu $\"{u}berzeugen$, aber or wirkte. In diesel Analyse wird die Rede von Hitler folgende Systematisierung $m\"{o}glich$: 1) Am Anfang weist Hitler auf die allgemeine Not hin. 2) Danach diffamiert or seine Gesner und provoziert starke Emotionen bei seinen $Zuh\"{o}rern$. 3) Zum $Schlu{\ss}$ $l\"{o}st$ Hitler bei den Deutschen eine starke Kampfbereitschaft aus und entwickelt vor semen $Zuh\"{o}rern$ seine Vision eines $bl\"{u}henden$, starken Deutschlands. 4) $Abschlie{\ss}end$ erkifirt Hitier seine $pers\"{o}nlichen$ ethischen Vorstellungen und seine sich daraus ergebenden Handlungen. Er liegt $gro{\ss}en$Wert darauf, die Ethik seine Handlungen zu $begr\"{u}nden$. Danach wird die Selbstdarstellung von Hitler beschrieben. $F\"{u}nf$ Realisierungsformen sind $daf\"{u}r$ relevant: a) $pers\"{o}nliche$ $Erz\"{a}hlungen$, b) Diffamierungen, c) sittlich wertvolle Ermahnungen, d) Taten und e) Ziele. Im Abschnitt drei wird die Rhetorik von Hitler gemacht. Hier handeit es sich um Ethos und Pathos. Hitler versuchte, die durch die Aktivierung zwischen ihm und Publikum vorhanden, $unbewu{\ss}ten$ psychischen Potentiate, die durch den Akt der Rede aktiviert werden, zu realisieren. Er hat jeder Sammlung nur gesagt, was sie $h\"{o}ren$ wollte, den wahren Sachverhalt nur auf $h\"{o}chst$ vordergryndige Weise.

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