• Title/Summary/Keyword: signaling chemical

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Bioinformatics Analysis of Hsp20 Sequences in Proteobacteria

  • Heine, Michelle;Chandra, Sathees B.C.
    • Genomics & Informatics
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    • v.7 no.1
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    • pp.26-31
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    • 2009
  • Heat shock proteins are a class of molecular chaperones that can be found in nearly all organisms from Bacteria, Archaea and Eukarya domains. Heat shock proteins experience increased transcription during periods of heat induced osmotic stress and are involved in protein disaggregation and refolding as part of a cell's danger signaling cascade. Heat shock protein, Hsp20 is a small molecular chaperone that is approximately 20kDa in weight and is hypothesized to prevent aggregation and denaturation. Hsp20 can be found in several strains of Proteobacteria, which comprises the largest phyla of the Bacteria domain and also contains several medically significant bacterial strains. Genomic analyses were performed to determine a common evolutionary pattern among Hsp20 sequences in Proteobacteria. It was found that Hsp20 shared a common ancestor within and among the five subclasses of Proteobacteria. This is readily apparent from the amount of sequence similarities within and between Hsp20 protein sequences as well as phylogenetic analysis of sequences from proteobacterial and non-proteobacterial species.

Hg2+-Selective Chemosensor Derived from 8-Hydroxyquinoline Having Benzothiazole Function in Aqueous Environment

  • Youk, Jin-Soo;Kim, Young-Hee;Kim, Eun-Jin;Youn, Na-Jin;Chang, Suk-Kyu
    • Bulletin of the Korean Chemical Society
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    • v.25 no.6
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    • pp.869-872
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    • 2004
  • Newly synthesized 8-hydroxyquinoline based benzothiazole derivative 2 showed a distinctive $Hg^{2+}$-selectivity over other transition metal ions in aqueous solution. The fluorescence emission at 455 nm of 2 was completely quenched upon interaction with $Hg^{2+}$ ions in dioxane-$H_2O$ system (9 : 1, v/v). The selectivity was decreased in the order of $Hg^{2+}\;>>\;Cu^{2+}\;>\;Cd^{2+}\;>\;Pb^{2+}\;{\thickapprox}\;Zn^{2+}\;{\thickapprox}\;Ni^{2+},\;and\;Hg^{2+}$ concentration dependent fluorescence quenching profile was observed in the presence of common interfering metal ions as background. The fluorescence behavior of 2 suggests that the prepared compound could be used as a fluorescent signaling subunit for the construction of new $Hg^{2+}$-sensitive ON-OFF type supramolecular switching systems.

Synthesis of Flavokawain Analogues and their Anti-neoplastic Effects on Drug-resistant Cancer Cells Through Hsp90 Inhibition

  • Seo, Young Ho;Park, Sun You
    • Bulletin of the Korean Chemical Society
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    • v.35 no.4
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    • pp.1154-1158
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    • 2014
  • Hsp90 is an ubiquitous molecular chaperone protein, which plays an important role in regulating maturation and stabilization of many oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 represents great promise as a therapeutic target of cancer. In this study, we synthesized flavokawain analogues and evaluated their biological activities against drug-resistant cancer cells. The study indicated that compound 1i impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975), down-regulated the expression of Hsp90 client proteins including EGFR, Her2, Met, Akt and Cdk4, and upregulated the expression of Hsp70. The result strongly suggested that compound 1i inhibited the proliferation of cancer cells through Hsp90 inhibition. Overall, compound 1i could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

Highly Selective Fluorescent Signaling for Al3+ in Bispyrenyl Polyether

  • Kim, Hyun-Jung;Kim, Su-Ho;Quang, Duong Tuan;Kim, Ja-Hyung;Suh, Il-Hwan;Kim, Jong-Seung
    • Bulletin of the Korean Chemical Society
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    • v.28 no.5
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    • pp.811-815
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    • 2007
  • A series of bispyrenyl-polyether have been synthesized and investigated as a fluorescent chemosensor for metal ions. The results showed that bispyrenyl-polyether system is selective towards Al3+ ion over other ions tested. In free ligand, excited at 343 nm, it displays a strong excimer emission at around 475 nm with a weak monomer emission at 375 nm. A ratiometry of monomer (375 nm) increase and excimer (475 nm) quenching was shown only when Al3+ ion is bound to ligand, because two facing pyrene groups form a less efficient overlap of π?π stacking compared with that of free ligand.

Chemical Modification of Transducin with Dansyl Chloride Hinders Its Binding to Light-activated Rhodopsin

  • Kosoy, Ana;Moller, Carolina;Perdomo, Deisy;Bubis, Jose
    • BMB Reports
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    • v.37 no.2
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    • pp.260-267
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    • 2004
  • Transducin (T), the heterotrimeric guanine nucleotide binding protein in rod outer segments, serves as an intermediary between the receptor protein, rhodopsin, and the effector protein, cGMP phosphodiesterase. Labeling of T with dansyl chloride (DnsCl) inhibited its light-dependent guanine nucleotide binding activity. Conversely, DnsCl had no effect on the functionality of rhodopsin. Approximately 2-3 mol of DnsCl were incorporated per mole of T. Since fluoroaluminate was capable of activating DnsCl-modified T, this lysine-specific labeling compound did not affect the guanine nucleotide-binding pocket of T. However, the labeling of T with DnsCl hindered its binding to photoexcited rhodopsin, as shown by sedimentation experiments. Additionally, rhodopsin completely protected against the DnsCl inactivation of T. These results demonstrated the existence of functional lysines on T that are located in the proximity of the interaction site with the photoreceptor protein.

Chemical Modification of Porcine Brain myo-Inositol Monophosphate Phosphatase by N-bromosuccinimide

  • Lee, Byung-Ryong;Bahn, Jae-Hoon;Jeon, Seong-Gyu;Ahn, Yoon-Kyung;Yoon, Byung-Hak;Kwon, Hyeok-Yil;Kwon, Oh-Shin;Choi, Soo-Young
    • BMB Reports
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    • v.32 no.3
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    • pp.294-298
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    • 1999
  • Myo-inositol monophosphate phosphatase is a key enzyme in the phosphoinositide cell-signaling system. Incubation of myo-inositol monophosphate phosphatase from porcine brain with N-bromosuccinimide (NBS) resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo-first-order kinetics with the second-order rate constant of $3.8{\times}10^3\;M^{-1}min^{-1}$. The time course of the reaction was significantly affected by the substrate myo-inositol-1-phosphate, which afforded complete protection against the loss of catalytic activity. Spectrophotometric studies indicated that about one oxindole group per molecule of enzyme was formed following complete loss of enzymatic activity. It is suggested that the catalytic function of myo-inositol monophosphate phosphatase is modulated by the binding of NBS to a specific tryptophan residue at or near the substrate binding site of the enzyme.

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Calcium Signaling of M II Oocyte during Chemical Activation of Calcium Ionopore and Cytochalasin B

  • Kim, Sung-Woo;Park, Jin-Ki;Park, Chun-Gyu;Lee, Ju-Young;Han, Joo-hee;Lee, Seung-Eun;Baek, Kyung-Nye;Chang, Won-Kyung
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.260-260
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    • 2004
  • The calcium ionophore (A23187) has been used for activation of porcine oocytes from in vitro maturation by many researches. The signaling of calcium was known to be a primary factor of activation of MII oocyte by calcium ionophore. The calcium level was measured by an intensity of fluo 4 fluorescence and confocal microscope. The level was increased by 7% ethanol or 70 μM calcium ionophore but oscillation was not found. (omitted)

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XRP44X Enhances the Cytotoxic Activity of Natural Killer Cells by Activating the c-JUN N-Terminal Kinase Signaling Pathway

  • Kim, Kwang-Soo;Park, Kyung-Soon
    • Development and Reproduction
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    • v.24 no.1
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    • pp.53-62
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    • 2020
  • Natural killer (NK) cells are innate lymphocytes that play an essential role in preventing cancer development by performing immune surveillance to eradicate abnormal cells. Since ex vivo expanded NK cells have cytotoxic activity against various cancers, including breast cancers, their clinical potential as immune-oncogenic therapeutics has been widely investigated. Here, we report that the pyrazole chemical XRP44X, an inhibitor of Ras/ERK activation of ELK3, stimulates NK-92MI cells to enhance cytotoxic activity against breast cancer cells. Under XRP44X stimulation, NK cells did not show notable apoptosis or impaired cell cycle progression. We demonstrated that XRP44X enhanced interferon gamma expression in NK-92MI cells. We also elucidated that potentiation of the cytotoxic activity of NK-92MI cells by XRP44X is induced by activation of the c-JUN N-terminal kinase (JNK) signaling pathway. Our data provide insight into the evaluation of XRP44X as an immune stimulant and that XRP44X is a potential candidate compound for the therapeutic development of NK cells.

Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions

  • Irfan, Muhammad;Kwak, Yi-Seong;Han, Chang-Kyun;Hyun, Sun Hee;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.538-543
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    • 2020
  • Cardiovascular diseases are a rapidly growing epidemic with high morbidity and mortality. There is an urgent need to develop nutraceutical-based therapy with minimum side effects to reduce cardiovascular risk. Panax ginseng occupies a prominent status in herbal medicine for its various therapeutic effects against inflammation, allergy, diabetes, cardiovascular diseases, and even cancer, with positive, beneficial, and restorative effects. The active components found in most P. ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds, which are considered to be the main pharmacologically active constituents in ginseng. P. ginseng is an adaptogen. That is, it supports living organisms to maintain optimal homeostasis by exerting effects that counteract physiological changes caused by physical, chemical, or biological stressors. P. ginseng possesses immunomodulatory (including both immunostimulatory and immunosuppressive), neuromodulatory, and cardioprotective effects; suppresses anxiety; and balances vascular tone. P. ginseng has an antihypertensive effect that has been explained by its vasorelaxant action, and paradoxically, it is also known to increase blood pressure by vasoconstriction and help maintain cardiovascular health. Here, we discuss the potential adaptogenic effects of P. ginseng on the cardiovascular system and outline a future research perspective in this area.

Cyclopamine, an Antagonist of Hedgehog (Hh) Signaling Pathway, Reduces the Hatching Rate of Parthenogenetic Murine Embryos

  • Park, Jaehyun;Moon, Jeonghyeon;Min, Sol;Chae, Stephan;Roh, Sangho
    • Journal of Embryo Transfer
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    • v.33 no.4
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    • pp.237-243
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    • 2018
  • Hedgehog (Hh) pathway plays a key role in development from invertebrate to vertebrate. It is known to be involved in cell differentiation, polarity, proliferation, including the development of vertebrate limb and the establishment of flies' body plan. To investigate how the regulation of Hh pathway affects the development of parthenogenetic murine embryos, the parthenogenetically activated murine embryos were treated with either cyclopamine (Cyc), an antagonist of Hh pathway, or purmorphamine, an agonist of Hh pathway. While Cyc did not affect the blastocyst formation and its total cell number, the chemical reduced the hatching rate of embryos and the expression levels of Fn1 mRNA. The results of the present study show the possibility that Cyc may affect the development of embryos at blastocyst stage by blocking Hh pathway and this may cause detrimental effect to the embryos at peri-, and post-implantation stages.