• Title/Summary/Keyword: metabolic regulation

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Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

  • Prabhu, Venugopal Vinod;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekharan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6215-6220
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    • 2013
  • Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

Effects of forskolin on secretion of insulin like growth factor-I in the perfused rat liver model (백서 간 관류모델에서 forskolin이 Insulin like growth factor-I의 분비에 미치는 효과)

  • Kang, Chang-won;Lee, Dae-yeol;Lee, Ho-il
    • Korean Journal of Veterinary Research
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    • v.39 no.5
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    • pp.938-944
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    • 1999
  • The insulin-like growth factor-I(IGF-I) is an important metabolic factor involved in cell growth and metabolism. Although secretion of IGF-I in rat liver is regulated by growth hormone, the effects of forskolin, adenylate cyclase activator, on secretion of IGF-I have not been reported. Therefore, a modified perfused rat liver model was used to investigate the regulatory effects of forskolin on IGF-I secretion in this experiment. The results were summerized as follows : 1. Modified perfused rat liver model was not changed to aspartate aminotransferase(AST), alanine aminotransferase(ALT) and lactic dehydrogenase(LDH) secretion in time. 2. The IGF-I secretion in hepatic cell was increased by forskolin($10^{-5}$, $10^{-6}$ and $10^{-7}M$) in a dose-dependent manner as compared with those of the controls, and significantly increased by $10^{-5}$ and $10^{-6}$ forskolin(p < 0.05). 3. Secretion of glucose in hepatic cell significantly was decreased by $10^{-5}$ forskolin as compared with those of controls(p < 0.05). These results suggest that forskolin may be involved in the regulation of IGF-I secretion in the perfused rat liver.

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Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells

  • Lee, Phil Young;Park, Byoung Chul;Chi, Seung Wook;Bae, Kwang-Hee;Kim, Sunhong;Cho, Sayeon;Kang, Seongman;Kim, Jeong-Hoon;Park, Sung Goo
    • BMB Reports
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    • v.49 no.10
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    • pp.560-565
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    • 2016
  • Granzyme A (GzmA) was first identified as a cytotoxic T lymphocyte protease protein with limited tissue expression. A number of cellular proteins are known to be cleaved by GzmA, and its function is to induce apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates during apoptotic cell death. Here, we demonstrated that histone H4 was cleaved by GzmA during staurosporine-induced cell death; however, in the presence of caspase inhibitors, staurosporine-treated Raji cells underwent necroptosis instead of apoptosis. Furthermore, histone H4 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. These results suggest that histone H4 is a novel substrate for GzmA in staurosporine-induced cells.

Anti-Obesity Drugs: A Current Research Insight

  • Son Eun-hwa;In San-Whan;Kim Byung-Oh;Pyo Suhkneung
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.89-101
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    • 2005
  • Obesity is increasing worldwide and has become a major health burden in Western societies affecting every third American and every fifth European. Obesity makes a major contribution to morbidity and mortality, predisposing individuals to cardiovascular disease and diabetes. Many new substances are currently being investigated for their usefulness in the pharmacotherapy of obesity. Most anti-obesity drugs can be divided into four groups: those that reduce food intake; those that alter metabolism; those that increase thermogenesis; and those that regulate hormone involved in feeding behavior. In this article we review these and other agents available in various countries for the treatment of obesity. Perhaps more importantly, we have focussed on areas of potential productivity in the future. Over the last 5 or so years, this impetus in obesity research has provided us with exciting new drugs targets involved in the regulation of feeding behavior and cellular mechanism involved in energy expenditure. Recent development in the quest for control of human obesity include the discovery of hormones, neuropeptides, receptors and transcription factors involved in feeding behavior, metabolic rate and adipocyte development. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individual different genetic and physiological basis of obesity. It remains the hope of research scientists that in the not too distant future we shall see a new class of anti-obesity drugs arising logically from the molecular biology revolutions.

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Rescue of Oxidative Stress by Molecular Chaperones in Yeast

  • Ueom Jeonghoon;Kang Sooim;Lee Kyunghee
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2002.10a
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    • pp.76-78
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    • 2002
  • Heat shock proteins (HSPs) are induced in most living cells by mild heat treatment, ethanol, heavy metal ions and hypoxia. In yeast Saccharomyces cerevisiae, mild heat pretreatment strongly induces Hsp104 and thus provide acquired thermotolerance. The ability of hsp104 deleted mutant $({\triangle}hsp104)$ to acquire tolerance to extreme temperature is severely impaired. In providing thermotolerance, two ATP binding domains are indispensible, as demonstrated in ClpA and ClpB proteases of E. coli. The mechanisms by which Hsp104 protects cells from severe heat stress are not yet completely elucidated. We have investigated regulation of mitochondrial metabolic pathways controlled by the functional Hsp104 protein using $^{13}C_NMR$ spectroscopy and observed that the turnover rate of TCA cycle was enhanced in the absence of Hsp104. Production of ROS, which are toxic to kill cells radiply via oxidative stress, was also examined by fluorescence assay. Mitochondrial dysfunction was manifested in increased ROS levels and higher sensitivity for oxidative stress in the absence of Hsp104 protein expressed. Finally, we have identified mitochondrial complex I and Ferritin as binding protein(s) of Hsp104 by yeast two hybrid experiment. Based on these observations, we suggest that Hsp104 protein functions as a protector of oxidative stress via either keeping mitochondrial integrity, direct binding to mitochonrial components or regulating metal-catalyzed redox chemistry.

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Effects of Chestnut Inner Shell Extract on 3T3-L1 Preadipocyte Differentiation (율피 추출물이 3T3-L1 지방전구세포 분화에 미치는 영향)

  • Lee, Seon-Goo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.2
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    • pp.266-271
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    • 2010
  • Obesity occurred by energy imbalance, is increasing regardless of race, sex, age, and related to the metabolic syndrome, diabetes and cardiovascular disease. Since adipose tissue plays a critical role in regulating energy homeostasis, understanding of adipogenesis pathway and finding of regulatory mechanism for adipogenesis can be helpful to manage obesity as well as obesity-related diseases. In this study, to investigate the effects of Chestnut Inner Shell(CIS) extract on the adipogenesis in 3T3-L1 preadipocytes, 3T3-L1 preadipocytes were differentiated with adipogenic reagents for 9 days in the absence or presence of CIS extract ranging from 10 - 100 ${\mu}g/m{\ell}$. The effect of CIS extract on 3T3-L1 differentiation was examined by measuring intracelluar lipid droplet and triglyceride contents. CIS extract remarkably inhibited lipid accumulation(about 45% inhibition at 100 ${\mu}g/m{\ell}$ of CIS extract) and slightly decreased triglyceride contents(about 15% decrease at 100 ${\mu}g/m{\ell}$ of CIS extract) in 3T3-L1 preadipocytes at the concentration showing no cytotoxicity. These results demonstrated that CIS extract significantly inhibit adipogenesis and can be used for the regulation of obesity.

Potential drug targets in the GPCR-$G{\alpha}_{12}/G{\alpha}_{13}$ signaling pathways

  • Kim, Sang-Geon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2008.04a
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    • pp.89-99
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    • 2008
  • GPCRs are large families of cell surface receptors that transmit signals through conformational changes upon ligand activation and an interaction with the heterotrimeric G-proteins. GPCRs regulate the cell-signaling pathways and participate in the regulation of physiological processes through the G-proteins defined by their ${\alpha}$ subunits. A family of 20 G protein-coupled receptors (GPCRs) that provide a large class of tractable drug targets for new anti-inflammatory drugs and, in certain instances, for the treatment of the inflammatory indications such as atherosclerosis, rhinitis, asthma, pulmonary disease and arthritis. In view of the important findings showing that $G{\alpha}_{12}/G{\alpha}_{13}$ regulate the various cellular processes such as actin-stress fiber formation, neurite retraction, platelet aggregation, gene induction, and apoptosis, we became interested in whether, after coupling to the activated GPCRs, the G-proteins and their downstream molecules might be involved in the pathologic processes of chronic inflammatory diseases (e.g., liver fibrosis). In this symposium, the possible link of the G-proteins with the pathophysiology will be discussed with the aim of finding potential new drug targets.

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Differentially Expressed Genes in Marine Medaka Fish (Oryzias javanicus) Exposed to Cadmium

  • Woo, Seon-Ock;Son, Sung-Hee;Park, Hong-Seog;Vulpe, Chris D.;Ryu, Jae-Chun;Yum, Seung-Shic
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.293-299
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    • 2008
  • To screen the differentially expressed genes in cadmuim-exposed marine medaka fish (Oryzias javanicus), a candidate marine test fish for ecological toxicity, the differential display polymerase chain reaction (DD-PCR) was carried out, since the genome-wide gene expression data are not available in this fish species yet. A total of 35 clones were isolated from cadmium-exposed fish and their nucleotide sequences were analyzed. The differentially expressed gene candidates were categorized to response to stimulus (3); ion binding (3); DNA binding (1); protein binding (6); carbohydrate binding (1); metabolic process (4); biological regulation (3); cellular process (2); protein synthesis (2); catalytic activity (2); sense of sight (1); immune (1); neurohormone (1); signaling activity (1); electron carrier activity (1) and others (3). For real-time quantitative RT-PCR, we selected catalase, glucose-6-phosphate dehydrogenase, heat shock protein 70, and metallothionein and confirmed that cadmium exposure enhanced induction of these four genes.

Changes in Biosynthesis of Glutathione and Taurine in Rat Liver Challenged with tert-Butylhydroperoxide (랫트 간에서 tert-Butylhydroperoxide 투여에 의한 글루타치온과 타우린의 생합성 변화)

  • Kim, Sun-Ju;Park, Hyun-Ah;Kim, Young-Chul
    • YAKHAK HOEJI
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    • v.53 no.6
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    • pp.314-320
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    • 2009
  • We examined metabolic conversion of cysteine into glutathione (GSH) and taurine in rat liver under oxidative stress. Administration of tert-butylhydroperoxide (t-BHP) into the portal vein of male rats resulted in a rapid elevation of serum sorbitol dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities, which decreased gradually in 24 hr. Hepatic cysteine concentration was reduced in 3 hr, and recovered progressively, reaching a level greater than 200% of the normal value in 24 hr. GSH was increased both in liver and blood at 9 hr after t-BHP challenge, whereas hypotaurine or taurine was not altered. $\gamma$-Glutamylcysteine synthetase (GCS) activity was increased from 9 hr after t-BHP treatment, but protein expression of the GCS-heavy subunit was not changed in liver. Activity or expression of cysteine dioxygenase was not affected by t-BHP treatment. Taken together, these data show that an acute oxidant challenge to the rats may induce upregulation of cysteine availability and GCS activity, resulting in an enhancement of hepatic GSH synthesis, but the increased cysteine level does not stimulate taurine synthesis via cysteine sulfinate pathway. It is indicated that the regulation of GSH and taurine biosynthesis from cysteine is not solely dependent on the cysteine concentration in rat liver under oxidative stress.

Hydrogen Fermentation of the Galactose-Glucose Mixture (갈락토스-글루코스 혼합당 수소 발효)

  • Cheon, Hyo-Chang;Kim, Sang-Youn
    • Journal of Hydrogen and New Energy
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    • v.23 no.4
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    • pp.397-403
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    • 2012
  • Galactose, an isomer of glucose with an opposite hydroxyl group at the 4-carbon, is a major fermentable sugar in various promising feedstock for hydrogen production including red algal biomass. In this study, hydrogen production characteristics of galactose-glucose mixture were investigated using batch fermentation experiments with heat-treated digester sludge as inoclua. Galactose showed a hydogen yield compatible with glucose. However, more complicated metabolic steps for galactose utilization caused a slower hydrogen production rate. The existence of glucose aggravated the hydrogen production rate, which would result from the regulation of galactose-utilizing enzymes by glucose. Hydrogen produciton rate at galactose to glucose ratio of 8:2 or 6:4 was 67% of the production rate for galactose and 33% for glucose, which could need approximately 1.5 and 3 times longer hydraulic retention time than galacgtose only condition and glucose only condition, respectively, in continuous fermentation. Hydrogen production rate, Hydrogen yield, and organic acid production at galactose to glucose ratio of 8:2 or 6:4 were 0.14 mL H2/mL/hr, 0.78 mol $H_2$/mol sugar, and 11.89 g COD/L, respectively. Galactose-rich biomass could be usable for hydogen fermenation, however, the fermentation time should be allowed enough.