• Title/Summary/Keyword: Iron chelator

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Anti-Proliferative Effect of Tetraphenylporphine (TPP) as an Iron Chelator on Vascular Smooth Muscle Cells and its Release Profiles from Polymer Coating Layer (철 킬레이터로서의 tetraphenylporphine의 혈관평활근세포의 성장억제효과와 고분자 코팅막으로부터의 방출 특성)

  • Park, Min-Hee;Kang, Soo-Yong;Park, Hyun-Jeong;Seo, Jin-Seon;Park, Young-A;Kim, Ji-Eun;Kim, Yang-Geun;Whang, Bae-Geon;Munkhjargal, Odonchimeg;Shim, Young-Key;Kho, Weon-Gyu;Lee, Woo-Kyoung
    • Journal of Pharmaceutical Investigation
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    • v.38 no.2
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    • pp.93-98
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    • 2008
  • The drug-eluting stent (DES) implantation is a widely acceptable treatment for coronary heart disease. It was reported that iron chelator had anti-proliferative effect on human vascular smooth muscle cells (HA-VSMCs). In this study, tetraphenylporphine (TPP) was selected as an iron chelator and drug for DES. MTT assay showed that TPP had antiproliferative effect on HA-VSMCs. TPP and polycaprolactone (PCL) were coated onto stainless steel plate using a spraycoating method. From the surface morphology examination of the coated plate by SEM, smooth polymer coating layer could be observed. The thickness of coating layer could be controlled by changing repeating time of coating. From in vitro release test, sustained release of TPP was observed from plate during two weeks. Thus, TPP as iron chelator can be used as drug for stent coating because of its antiproliferative effect and sustain release profile.

Iron Chelator-Inducible Expression System for Escherichia coli

  • Lim, Jae-Myung;Hong, Mi-Ju;Kim, Seong-Hun;Oh, Doo-Byoung;Kang, Hyun-Ah;Kwon, Oh-Suk
    • Journal of Microbiology and Biotechnology
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    • v.18 no.8
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    • pp.1357-1363
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    • 2008
  • The $P_{entC}$ promoter of the entCERA operon encoding enzymes for enterobactin biosynthesis in Escherichia coli is tightly regulated by the availability of iron in the culture medium. In iron-rich conditions, the $P_{entC}$ promoter activity is strongly repressed by the global transcription regulator Fur (ferric uptake regulator), which complexes with ferrous ions and binds to the Fur box 19-bp inverted repeat. In this study, we have constructed the expression vector pOS2 containing the $P_{entC}$ promoter and characterized its repression, induction, and modulation by quantifying the expression of the lacZ reporter gene encoding $\beta$-galactosidase. $\beta$-Galactosidase activities of E. coli transformants harboring pOS2-lacZ were highly induced in the presence of divalent metal ion chelators such as 2,2'-dipyridyl and EDTA, and were strongly repressed in the presence of excess iron. It was also shown that the basal level $\beta$-galactosidase expression by the $P_{entC}$ promoter was drastically decreased by incorporating the fur gene into the expression vector. Since the newly developed iron chelator-inducible expression system is efficient and cost-effective, it has wide applications in recombinant protein production.

Peroxidase Activity of Cytochrome c

  • Kim, Nam-Hoon;Jeong, Moon-Sik;Choi, Soo-Young;Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.25 no.12
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    • pp.1889-1892
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    • 2004
  • The peroxidase activity of cytochrome c was studied by using a chromogen, 2,2'-azinobis-(2-ethylbenzthiazoline-6-sulfonate) (ABTS). Initial rate of ABTS oxidation formation was linear with respect to the concentration of cytochrome c between 2.5-10 ${\mu}$M and $H_2O_2$ between 0.1-0.5 mM. The optimal pH for the peroxidase activity of cytochrome c was 7.0-8.5. The peroxidase activity retained about 40% of the maximum activity when exposed at 60 $^{\circ}C$. for 10 min. The peroxidase activity showed a typical Michaelis-Menten kinetics for $H_2O_2$ which Km value was 29.6 mM. Radical scavengers inhibited the peroxidase activity of cytochrome c. The peroxidase activity was significantly inhibited by the low concentration of iron chelator, deferoxamine. The results suggested that the peroxidase activity was associated with iron in the heme of cytochrome c.

Effects of the microbiological properties and pathogenicity of Photobacterium damselae subsp. damselae under different culture conditions (배양 조건이 Photobacterium damselae subsp. damselae의 미생물학적 성상 및 병원성에 미치는 영향)

  • Kwon, Mun-Gyeong;Cho, Byoung-Youl;Park, Myeong-Ae
    • Journal of fish pathology
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    • v.22 no.3
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    • pp.239-251
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    • 2009
  • The effects of microbiological properties and pathogenicity of Photobacterium damselae subsp. damselae were investigated under different culture conditions, temperature, pH, NaCl and iron concentration on culture media. Favorable conditions for bacterial growth were between 15-30${^{\circ}C}$, pH 5-9, 0-4% NaCl concentration and iron contents of over 10 mM, whereas the bacterial growth was inhibited under iron chelator existence. When P. damselae was cultured in iron-limited tryptic soy broth, total protein concentration of extracellular products, cytotoxic ability of ECPs on cell line, bacterial viability in flounder serum, phospholipase and siderophore activities of ECPs were significantly increased. On the other hand, the activities of P. damselae cultured under iron-added conditions were decreased. In this study, the iron-limited conditions were similar to the host in which iron concentration is low. During infection caused by P. damselae, the conditions could be related to the pathogenesis of the pathogen.

Enhancement of Methylene Blue-induced Cytotoxicity in Human Brain Tumor Cells by an Iron Chelator, Deferoxamine

  • Lee, Yong-Soo;Han, Suk-Kyu;Wurster, Robert D.
    • Archives of Pharmacal Research
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    • v.18 no.3
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    • pp.159-163
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    • 1995
  • Previously, we have reported that methylene blue (MB) induces cytotoxicity in human brain tumor cells through the generation of free radicals. In this study the effect of deferoxamine (DFO), an iron chelator, on MB-induced cytotoxicity was investigated using SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cells as model cellular systems. The cytotoxic effect of MB was potentiated by DFO. The potentiation effect of DFO was significantly blocked by either stoichiometric amounts of ferric ion, various antioxidants, hydroxyl radical scavengers or intracellular $Ca^{2+}$ release blockers. These results suggest that hydroxyl radical and intracellular $Ca^{2+}$ may act as important mediators of the enhanced cytotoxicity by MB and DFO. These results further suggest that the combined treatment with MB and DFO may be useful for the therapeutical applications of human brain tumors.

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Temperature dependent 2,3-dihydroxybenzoic acid production in Acinetobacter sp. B-W (Acinetobacter sp. B-W의 온도 의존적 2,3-dihydroxybenzoic acid 생산)

  • Kim, Kyoung-Ja;Lee, Jae-Hun;Yang, Yong-Joon
    • Korean Journal of Microbiology
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    • v.51 no.3
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    • pp.249-255
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    • 2015
  • A soil microorganism producing iron chelator (siderophore) under low iron stress (up to $2{\mu}M$ of iron) was identified as Acinetobacter sp. B-W by 16S rDNA sequence analysis, biochemical-, physiological tests and morphological analysis using electron microscope. Catechol nature of siderophore was detected by Arnow test. Although optimal cell growth was identified at $36^{\circ}C$ in iron-limited media, significant quantities of siderophore were produced only at $28^{\circ}C$. Biosynthesis of siderophore was strongly inhibited by growth at $36^{\circ}C$. Production of siderophore was completely inhibited by $10{\mu}M\;FeCl_3$. Iron chelator produced from Acinetobacter sp. B-W was purified from supernatant using butanol extraction, Sephadex LH-20 column chromatography and HPLC. Purified sideropore was identified as 2,3-dihydroxybenzoic acid by HPLC, TLC and IR analysis.

Measurement of Iron-dependence of pupA Promoter Activity by a pup-lux Bioreporter

  • Khang, Yong-Ho;Yang, Zamin-K.;Burlage, Robert-S.
    • Journal of Microbiology and Biotechnology
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    • v.7 no.5
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    • pp.352-355
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    • 1997
  • The promoter region of the pupA gene of Pseudomonas putida WCS358 was fused with the structural genes for bioluminescence (luxCDABE) from Vibrio fischeri, and the resulting fusion plasmid harbored by the WCS358 host. The pup-lux fusion gene was then used for quantitative analysis of the iron-dependence of pupA promoter activity. Factors affecting bioluminescence produced by the pup-lux bioreporter were found to be cell activity, iron-chelator concentrations, Fe(III) concentrations, and nutrient components. Light production rates of the pup-lux bioreporter were inversely dependent upon iron molecules when $FeCl_3$ concentrations were between $10^{-2}$ and 1 ${\mu}M$ in nutrient-poor minimal media, and between 0.1 and 10 mM in nutrient-rich complex media.

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Salsolinol, a catechol neurotoxin, induces oxidative modification of cytochrome c

  • Kang, Jung Hoon
    • BMB Reports
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    • v.46 no.2
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    • pp.119-123
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    • 2013
  • Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin, is known to perform a role in the pathogenesis of Parkinson's disease (PD). In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with salsolinol. When cytochrome c was incubated with salsolinol, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in salsolinol-treated cytochrome c. Salsolinol also led to the release of iron from cytochrome c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the salsolinol-mediated cytochrome c modification and carbonyl compound formation. It is suggested that oxidative damage of cytochrome c by salsolinol might induce the increase of iron content in cells, subsequently leading to the deleterious condition which was observed. This mechanism may, in part, provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD.

Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

  • Kang, Jung Hoon
    • Bulletin of the Korean Chemical Society
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    • v.34 no.11
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    • pp.3295-3300
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    • 2013
  • Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

Oxidative Modification of Cytochrome c by Tetrahydropapaveroline, an Isoquinoline-Derived Neurotoxin

  • Kang, Jung Hoon
    • Bulletin of the Korean Chemical Society
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    • v.34 no.2
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    • pp.406-410
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    • 2013
  • Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.