• Title/Summary/Keyword: Hydrogen pathway

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Agmatine Reduces Hydrogen Peroxide in Mesangial Cells under High Glucose Conditions

  • Lee, Geun-Taek;Ha, Hun-Joo;Lee, Hyun-Chul;Cho, Young-Dong
    • BMB Reports
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    • v.36 no.3
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    • pp.251-257
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    • 2003
  • Agmatine, an amine and organic cation, reduced $H_2O_2$ that was generated by hyperglycemia, and transcription factors such as NF-${\kappa}B$ and AP-1 activity in the mesangial cells that were exposed to high glucose. However, spermine which shares a strong nucleophilic structure with agmatine decreased the $H_2O_2$ levels and AP-1, but not the NF-${\kappa}B$ activity. Possible roles for agmatine and spermine in decreasing fibronectin are discussed, and the signaling pathway for agmatine-reduced fibronectin accumulation is presented.

Dimerization of Fibril-forming Segments of α-Synuclein

  • Yoon, Je-Seong;Jang, Soon-Min;Lee, Kyung-Hee;Shin, Seok-Min
    • Bulletin of the Korean Chemical Society
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    • v.30 no.8
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    • pp.1845-1850
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    • 2009
  • We have performed replica-exchange molecular dynamics (REMD) simulations on the dimer formation of fibrilforming segments of $\alpha$-Synuclein (residues 71 - 82) using implicit solvation models with two kinds of force fields- AMBER parm99SB and parm96. We observed spontaneous formation of dimers from the extensive simulations, demonstrating the self-aggregating and fibril forming properties of the peptides. Secondary structure profile and clustering analysis showed that dimers with antiparallel $\beta$-sheet conformations, stabilized by well-defined hydrogen boding, are major species corresponding to global free energy minimum. Parallel dimers with partial $\beta$-sheets are found to be off-pathway intermediates. The relative instability of the parallel arrangements is due to the repulsive interactions between bulky and polar side chains as well as weaker backbone hydrogen bonds.

Adhesion-induced generation of oxygen free radical from human alveolar macrophages and its mechanisms (폐포대식세포의 부착에 의한 산소유리기 분비능 활성화 및 그 기전)

  • Chung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.210-220
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    • 1996
  • Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

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N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

  • Lee, Daewoo;Kook, Sung-Ho;Ji, Hyeok;Lee, Seung-Ah;Choi, Ki-Choon;Lee, Kyung-Yeol;Lee, Jeong-Chae
    • BMB Reports
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    • v.48 no.11
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    • pp.636-641
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    • 2015
  • There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC.

Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1 signaling pathway

  • Zhang, Baoshun;Yu, Deqing;Luo, Nanxuan;Yang, Changqing;Zhu, Yurong
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.373-384
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    • 2020
  • Paeonol, quercetin, β-sitosterol, and gallic acid extracted from Moutan Cortex had been reported to possess anti-oxidative, anti-inflammatory, and anti-tumor activities. This work aimed to illustrate the potential anti-oxidative mechanism of monomers in human liver hepatocellular carcinoma (HepG2) cells-induced by hydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect of monomers was independence or synergy in mice stimulated by carbon tetrachloride (CCl4). Monomers protected against oxidative stress in HepG2 cells in a dose-response manner by inhibiting the generation of reactive oxygen species, increasing total antioxidant capacity, catalase and superoxide dismutase (SOD) activities, and activating the antioxidative pathway of nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that the in vitro antioxidant capacities of paeonol and quercetin were better than those of β-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levels of alanine transaminase and aspartate aminotransferase, augmented the contents of glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1 proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, β-sitosterol, and gallic acid play a defensive role against H2O2-induced oxidative stress through activating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidative properties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotective effects, which is independent rather than synergy.

Pyrolytic Reaction Pathway of Chloroethylene in Hydrogen Reaction Atmosphere (수소 반응분위기에서 Chloroethylene 열분해 반응경로 특성)

  • Won, Yang-Soo
    • Korean Chemical Engineering Research
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    • v.49 no.5
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    • pp.510-515
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    • 2011
  • The pyrolytic reaction of 1,1-dichloroethylene($CH_2CCl_2$) has been conducted to investigate thermal decomposition of chlorocarbon and product formation pathways under hydrogen reaction environment. The reactions were studied in a isothermal tubular flow reactor at 1 atm total pressure in the temperature range $650{\sim}900^{\circ}C$ with reaction times of 0.3~2.0 sec. A constant feed molar ratio $CH_2CCl_2:H_2$ of 4:96 was maintained through the whole experiments. Complete decay(99%) of the parent reagent, $CH_2CCl_2$ was observed at temperature near $825^{\circ}C$ with 1 sec. reaction time. The important decay of $CH_2CCl_2$ under hydrogen reaction environment resulted from H atom cyclic chain reaction by abstraction and addition displacement. The highest concentration (28%) of $CH_2CHCl$ as the primary product was observed at temperature $700^{\circ}C$, where up to 46% decay of $CH_2CCl_2$ was occurred. The secondary product, $C_2H_4$ as main product was detected at temperature above $775^{\circ}C$. The one less chlorinated ethylene than parent increase with temperature rise subsequently. The HCl and dechlorinated hydrocarbons such as $C_2H_4$, $C_2H_6$, $CH_4$ and $C_2H_2$ were the main products observed at above $825^{\circ}C$. The important decay of $CH_2CCl_2$ resulted from H atom cyclic chain reaction by abstraction and addition displacement. The important pyrolytic reaction pathways to describe the features of reagent decay and intermediate product distributions, based upon thermochemical and kinetic principles, were suggested.

Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes

  • Kim, Ki-Cheon;Kang, Sam-Sik;Lee, Jong-Sung;Park, Deok-Hoon;Hyun, Jin-Won
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.57-61
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    • 2012
  • The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

Analysis of Parameters for the Off-Site Dose Calculation Due to HTO, oBT, and Radioactive Carbon Ingestion (국내 원자력발전소 주변 삼중수소 및 $^14C$ 섭취선량 평가 경로인자 분석)

  • 이갑복;정양근;방선영;엄희문
    • Proceedings of the Korean Radioactive Waste Society Conference
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    • 2004.06a
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    • pp.361-367
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    • 2004
  • For assessment of tritium and radiocarbon ingestion dose to off site individuals, water, hydrogen, and carbon content of main farm produce of Korea were investigated to replace the existing data in K-DOSE60, the Offsite Dose Calculation Manual (ODCM) of Korea Hydro & Nuclear Power Co. Ltd, (KHNP). Main items and weighting factors of farm produce were determined with the nationwide food intake data in 2001, 2002. Main farm produce were sampled around Kori, Wolsong, Ulchin, Younggwang nuclear power sites, Content of each produce was multiplied by weighting factor and summed up to make the weighted mean group value For grains, water, hydrogen, and carbon content was not much different from the existing data currently used in K-DOSE60, but root vegetables had 3.5 times more hydrogen, and leafy vegetables and fruits had 0.7∼1.3 times more or less water, hydrogen, and carbon contents than K-DOSE60.

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Hydrogen sulfide restores cardioprotective effects of remote ischemic preconditioning in aged rats via HIF-1α/Nrf2 signaling pathway

  • Wang, Haixia;Shi, Xin;Cheng, Longlong;Han, Jie;Mu, Jianjun
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.3
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    • pp.239-249
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    • 2021
  • The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

Metabolic Flux Shift of Weissella kimchii sk10 Grown Under Aerobic Conditions

  • Park, Sun-Mi;Kang, Hye-Sun;Park, Doo-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.14 no.5
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    • pp.919-923
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    • 2004
  • The sk10 isolated from kimchi was identified as W. kimchii on the basis of l6s-rDNA sequencing. Studies were made to analyze the metabolic flux shift of the sk10 on glucose under aerobic growth conditions. The sk10 produced 38.2 mM acetate, 16.3 mM ethanol, and 33.2 mM lactate under aerobic conditions, but 2.4 mM acetate, 48.0 mM ethanol, and 44.1 mM lactate under anaerobic conditions. The NADH peroxidase (NADH-dependent hydrogen peroxidase) activity of sk10 grown under aerobic conditions was 11 times higher than that under anaerobic conditions. Under the low ratio of $NADH/NAD^+$, the metabolic flux toward lactate and ethanol was shifted to the flux through acetate kinase without NADH oxidation. The kinds of enzymes and metabolites of sk10 were close to those in the pathway of Leuconostoc sp., but the metabolites produced under aerobic growth conditions were different from those of Leuconostoc sp. The stoichiometric balance calculated using the concentrations of metabolites and substrate was about 97%, coincident with the theoretical values under both aerobic and anaerobic conditions. From these results, it was concluded that the metabolic flux of W. kimchii sk10 was partially shifted from lactate and ethanol to acetate under aerobic conditions only.