• Title/Summary/Keyword: Molecular radicals

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Overview on Molecular Toxicological Aspects of Helicobacter pylori Virulence Factor, Cytotoxin-associated Antigen A (CagA) (헬리코박터 파이로리의 병원성 단백질, CagA에 대한 분자 독성학적 측면에서의 고찰)

  • Kim Byung J.;Jung Hwa Jin;Hwang Jee Na;Kang Seok Ha;Oh Se-Jin;Seo Young Rok
    • Toxicological Research
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    • v.20 no.3
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    • pp.179-185
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    • 2004
  • Helicobacter pylori (H. pylori) infects more than half of the people in the world as a major microbe to cause most of gastric diseases. Recently, cytotoxin associated-antigen A (CagA) is believed as one of the most important virulence factors of H. pylori. Molecular toxicological pathway of CagA is necessary to investigate for understanding the pathological and toxicological aspects of H. pylori, since this virulence protein harasses intercellular processes of host cells to get profit for the survival of H. pylori. CagA is coded from cag pathogenicity island (cag PAI) and translocated into host cells by Type 4 secretion system (TFSS). Tyrosine phosphorylation of CagA targets Src homology 2-containing phosphotyrosine phosphatase (SHP-2) to form a CagA-SHP-2 complex. This complex depends on the similarity of sequence between EPIYA motif and Src homology 2 domain (SH2 domain) of CagA. The generation of growth factors is an essential role of CagA in protecting and healing gastric mucosa for the survival of H. pylori. On the other hand, the activation of IL-8 by CagA induces neutrophils generating inflammation and free radicals. Indeed, free radicals are well known carcinogen to induce DNA damage. In addition, the transduction of mitogen-activation signal by CagA is one of the interesting features to understand how to cause cancer. The relationship between cancer and inflammation with CagA was mainly discussed in this review.

The Role of Fungal Laccase in Biodegradation of Lignin

  • Andrzej Leonowicz;Jolanta Luterek;Maria W.Wasilewska;Anna Matuszewska;M.Hofrichter;D.Ziegenhagen;Jerzy Rogalski;Cho, Nam-Seok
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.31 no.5
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    • pp.1-11
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    • 1999
  • Wood components, cellulose and lignin, are degraded simultaneously and the general outline for the complementary character of carbohydrates and lignin decomposition as well as the existence of enzymatic systems combining these processes is still valid. The degradatiion of free cellulose or hemicellulose into monosaccharides has long been known to be relatively simple, but the mechanism of lignin degradatiion wasn ot solved very clearly yet. Anyway the biodegradation of woold constituents is understood at present as an enzymatic process. Kigninolytic activity has been correlated with lignin and manganese peroxidases. At present the attention is paid to laccase. Laccase oxidizes lignin molecule to phenoxy radicals and quinones . This oxidation can lead to the cleavageo f C-C or C-O bonds in the lignin phenyl-propane subunits, resulting either in degradation of both side chains and aromatic rings, or in demethylation processes. The role of laccase lies in the "activation" of some low molecular weight mediators and radicals produced by fungal cultures. Such activated factors produced also in cooperation with other enzymes are probably exported to the wood environment where they work in degradation processes as the ' enzyme messengers." It is worth mentioning that only fungi possessing laccase show demethylating activity. Thus demethylation, the process important for ligninolysis, is probably caused exclusively by laccase. Under natural conditions laccase seems to work with other fungal enzymes , mediators and mediating radicals. It has shown the possibility of direct Bjrkman lignin depolymerization by cooperative activity of laccase and glucose oxidase.

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Ethanol Eluted Extract of Rhus verniciflua Stokes Showed both Antioxidant and Cytotoxic Effects on Mouse Thymocytes Depending on the Dose and Time of the Treatment

  • Lee, Jeong-Chae;Kim, Ju;Lim, Kye-Taek;Yang, Moon-Sik;Jang, Yong-Suk
    • BMB Reports
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    • v.34 no.3
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    • pp.250-258
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    • 2001
  • For a long time Rhus verniciflua Stokes (RVS) has traditionally been used as a herbal plant. It is known to contain various biological activities. Previously, a crude ethanol extract from RVS was reported to have antioxidant effects, and antiproliferative activities, on human cancer cell lines. In this report, we prepared a highly purified ethanol extract from RVS, which did not contain the urushiol derivatives, named REEE-1 ($\underline{R}$hus $\underline{e}$thanol $\underline{e}$luted $\underline{e}$xtract-1), to investigate the mechanisms of the scavenging activity of hydroxyl radicals using mouse thymocytes. The results from the deoxyribose, DNA nicking, and glucose/glucose oxidase enzyme assays showed that REEE-1 contained a strong scavenging activity of oxygen free radicals, especially of hydroxyl radicals. However, interestingly, REEE-1 also showed cytotoxicity against the thymocytes, although the effect was variable, depending on the concentrations and times of treatment. The REEE-1-mediated cytotoxicity against thymocytes, which has been used as one of the well-characterized models for apoptosis studies, was verified to be apoptotic. This was proven by the following: the appearance of DNA laddering, increases in DNA fragmentation, low fluorescence intensity in the nuclei after propidium iodide staining, and positive Annexin V staining of the cells. These results suggested that REEE-1 had both antioxidative activity and cytotoxicity against the thymocytes, although the effect of the cytotoxicity was variable, depending on the dose and time of the treatment.

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Oxidative Damage of DNA Induced by the Cytochrome c and Hydrogen Peroxide System

  • Kim, Nam-Hoon;Kang, Jung-Hoon
    • BMB Reports
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    • v.39 no.4
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    • pp.452-456
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    • 2006
  • To elaborate the peroxidase activity of cytochrome c in the generation of free radicals from $H_2O_2$, the mechanism of DNA cleavage mediated by the cytochrome c/$H_2O_2$ system was investigated. When plasmid DNA was incubated with cytochrome c and $H_2O_2$, the cleavage of DNA was proportional to the cytochrome c and $H_2O_2$ concentrations. Radical scavengers, such as azide, mannitol, and ethanol, significantly inhibited the cytochrome c/$H_2O_2$ system-mediated DNA cleavage. These results indicated that free radicals might participate in the DNA cleavage by the cytochrome c and $H_2O_2$ system. Incubation of cytochrome c with $H_2O_2$ resulted in a time-dependent release of iron ions from the cytochrome c molecule. During the incubation of deoxyribose with cytochrome c and $H_2O_2$, the damage to deoxyribose increased in a time-dependent manner, suggesting that the released iron ions may participate in a Fenton-like reaction to produce $\cdot$OH radicals that may cause the DNA cleavage. Evidence that the iron-specific chelator, desferoxamine (DFX), prevented the DNA cleavage induced by the cytochrome c/$H_2O_2$ system supports this mechanism. Thus we suggest that DNA cleavage is mediated via the generation of $\cdot$OH by a combination of the peroxidase reaction of cytochrome c and the Fenton-like reaction of free iron ions released from oxidatively damaged cytochrome c in the cytochrome c/$H_2O_2$ system.

Estimated Photodegradation Properties of Acetanilide Using AOPWIN (AOPWIN을 이용한 Acetanilide의 광부해 특성 평가)

  • 권민정;최윤호;송상환;박혜연;구현주;전성환;나진균;박광식
    • Environmental Analysis Health and Toxicology
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    • v.16 no.3
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    • pp.139-142
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    • 2001
  • Acetanilide is a High Production Volume Chemical, which is produced about 2,300 tons/year in Korea as of 1998 survey. Most is used as an intermediate for synthesis of pharmaceuticals and dyes, and the chemical is one of seven chemicals of which human and environmental risk are being assessed by National Institute of Environmental Research under the frame of OECD SIDS program. The Atmospheric Oxidation Program for Microsoft Windows (AOPWIN) is used to estimates the rate constant for the atmospheric, gas-phase reaction between photochemically produced hydroxyl radicals and organic chemicals. It is also used to estimates the rate constant for the gas-phase reaction between ozone and olefinic/acetylenic compounds. The rate constants estimated by the program are then used to calculate atmospheric half-lives for organic compounds based upon average atmospheric concentrations of hydroxyl radicals and ozone. AOPWIN requires only a chemical structure to make these predictions. Structures are entered into AOPWIN by SMILES (Simplified Molecular Input Line Entry System) notations. In this study, one of environmental fate/distribution of the chemical elements, photodegradation of acetanilide was estimated using AOPWIN model based on SMILES notation and chemical name data.

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Oxidative Modification of Cytochrome c by Hydrogen Peroxide

  • Kim, Nam Hoon;Jeong, Moon Sik;Choi, Soo Young;Kang, Jung Hoon
    • Molecules and Cells
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    • v.22 no.2
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    • pp.220-227
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    • 2006
  • Oxidative alteration of mitochondrial cytochrome c has been linked to disease and is one of the causes of proapoptotic events. We have investigated the modification of cytochrome c by $H_2O_2$. When cytochrome c was incubated with $H_2O_2$, oligomerization of the protein increased and the formation of carbonyl derivatives and dityrosine was stimulated. Radical scavengers prevented these effects suggesting that free radicals are implicated in the $H_2O_2$-mediated oligomerization. Oligomerization was significantly inhibited by the iron chelator, deferoxamine. During incubation of deoxyribose with cytochrome c and $H_2O_2$, damage to the deoxyribose occurred in parallel with the release of iron from cytochrome c. When cytochrome c that had been exposed to $H_2O_2$ was analyzed by amino acid analysis, the tyrosine, histidine and methionine residues proved to be particularly sensitive. These results suggest that $H_2O_2$-mediated cytochrome c oligomerization is due to oxidative damage resulting from free radicals generated by a combination of the peroxidase activity of cytochrome c and the Fenton reaction of free iron released from the oxidatively-damaged protein.

Free Radical Polymerization Algorithm for a Thermoplastic Polymer Matrix : A Molecular Dynamics Study (무정형 열가소성 고분자의 자유 라디칼 중합 분자동역학 시뮬레이션 알고리즘)

  • Jung, Ji-Won;Park, Chan-Wook;Yun, Gun-Jin
    • Composites Research
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    • v.32 no.3
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    • pp.163-169
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    • 2019
  • In this paper, we constructed a molecular dynamics (MD) polymer model of PMMA with 95% of conversion by using dynamic polymerization algorithm of a thermoplastic polymer based on free radical polymerization. In this algorithm, we introduced a united-atom level coarse-grained force field that combines the non-bonded terms from the TraPPE-UA force field and the bonded terms from the PCFF force field to alleviate the computation efforts. The molecular weight distribution and the average molecular weight of the polymer were calculated by investigating each chain generated from the free radical polymerization simulation. The molecular weight of the polymer was controlled by the number of initiator radicals presented in the initial state and molecular weight effect to the density, the glass transition temperature, and the mechanical properties were studied.

Mechanical Properties of Ultra-High Molecular Weight Polyethylene Irradiated with Gamma Rays

  • Lee, Choon-Soo;Yoo, Seung-Hoo;Jho, Jae-Young;Park, Kuiwon;Hwang, Tae-Won
    • Macromolecular Research
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    • v.12 no.1
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    • pp.112-118
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    • 2004
  • With the goal of enhancing the creep resistance of ultra-high molecular weight polyethylene (UHMWPE), we performed gamma irradiation and post-irradiation annealing at a low temperature, and investigated the crystalline structures and mechanical properties of the samples. Electron spin resonance spectra reveal that most of the residual radicals are stabilized by annealing at 100$^{\circ}C$ for 72 h under vacuum. Both the melting temperature and crystallinity increase after increasing the dose and by post-irradiation annealing. When irradiated with the same dose, the quenched sample having a higher amorphous fraction exhibits a lower swell ratio than does the slow-cooled sample. The measured tensile properties correlate well to the crystalline structure of the irradiated and annealed samples. For enhancing creep resistance, high crystallinity appears to be more critical than a high degree of crosslinking.

The Alcohol-inducible form of Cytochrome P450 (CYP 2E1): Role In Toxicology and Regulation of Expression

  • Novak, Raymond F.;Woodcroft, Kimberley J.
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.267-282
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    • 2000
  • Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

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Hypolipidemic Effects of Glycoprotein Isolated from Ficus Carica Linnoeus in Mice (무화과 당단백질의 혈중지질 저하 효과)

  • Lim, Kye-Taek;Lee, Sei-Jung;Ko, Jeong-Hyeon;Oh, Phil-Sun
    • Korean Journal of Food Science and Technology
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    • v.37 no.4
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    • pp.624-630
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    • 2005
  • Glycoprotein (60 kDa) isolated from Ficus Carica Linnoeus (FCL glycoprotein) was examined by evaluating its hypolipidemic effects on plasma cholesterol levels and hepatic detoxicant enzyme activities in ICR mice. FCL glycoprotein $(100{\mu}g/mL)$ had strong scavenging activities (38%) against lipid peroxyl radicals. When mice were treated with Triton WR-1339 (400 mg/kg), levels of total cholesterol (TC) and low-density lipoprotein (LDL)-cholesterol in plasma significantly increased by 53.9 and 47.5 mg/dL, respectively, compared to the control, whereas, when pretreated with FCL glycoprotein $(100{\mu}g/mL)$, decreased remarkably by 55.4, and 47,0 mg/dL, compared to Triton WR-1339 treatment alone. Interestingly, high-density lipoprotein (HDL)-cholesterol level did not change. Body and liver weights did not change significantly after Triton WR-1339 treatment in presence of FCL glycoprotein. FCL glycoprotein $(100{\mu}g/mL)$ stimulated activities of antioxidative detoxicant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), whereas GPx activity significantly increased compared to the control. These results suggest FCL glycoprotein has abilities to scavenge lipid peroxyl radicals, lower plasma lipid levels, and stimulate detoxicant enzyme activity in mouse liver.