• Title/Summary/Keyword: molecular pathogenesis

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Partial Characterization of Proteases from Culture Filtrate of Mycobacterium tuberculosis

  • Na, Byoung-Kuk;Song, Chul-Yong;Park, Young-Kill;Bai, Gill-Han;Ki, Sang-Jae
    • Journal of Microbiology
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    • v.34 no.2
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    • pp.198-205
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    • 1996
  • Two proteases were partially characterized from culture filtrate of Mycobacterium, tuberculosis KIT110. Their molecular weights were approximately 200 and 180 kDa, respectively and they exhibited similar enzymatic characteristics. These enzymes were inhibited significantly by EDTA and to some extent by EGTA. Their activity was enhanced by $Ca^{2+}$ and $Mg^{2+}$ to some degree. However, $Cu^{2+}$ and $Ag^{2+}$ completely inhibited the enzyme activity at the concentration of 2.5 and 5 mM, respectively. The optimal pH was 7.0 and optimal temperature was around $40^{\circ}C$. These enzymes were rapidly inactivated at $80^{\circ}C$. Therefore, they were heat-labile, neutral metalloproteases. These enzymes exhibited antigenicity shown by their reacting with sera from the partients with pulmonary tuberculosis. These enzymes were able to degrade serum proteins including hemoglobin, bovine serum albumin, lysozyme and immunoglobulin G and structural matrix protein such as type I collagen. Therefore, these enzymes may be thought to contribute to tissue necrosis and pathogenesis during infection.

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Antioxidative Effects of Flavonoids toward Modification of Human Low Density Lipoprotein (플라보노이드에 의한 사람 Low Density Lipoprotein 변형에 대한 항산화 효과)

  • 류병호
    • The Korean Journal of Food And Nutrition
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    • v.12 no.3
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    • pp.320-327
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    • 1999
  • The flavonoids are one of the most numberous and widespread groups of natural consituents. The low molecular weight of benzo-${\gamma}$-pyrone derivative are ubiquitous in plants and are vegetables nuts, seeds, leaves, flowers, and bark. The flavonoids constitute of a large class of compounds ubiquitous in plants containing a number of phenolic hydroxyl groups attached to ring structures conferring the antioxidant activity. Epidemiologic studies suggest that the dietary intake of antioxidants constitutes a risk factor for vasclar disease indicating that oxidation may be important in the pathogenesis of human athero-sclerosis. Elevated plasma low density lipoprotein (LDL) cholesterol concentration are associated with accelerated atherosclerosis, LDL is oxidized by smooth muscle cells resulting in several chemicals and physical changes of LDL. Oxidized LDL is responsible for cholesterol loading of macrophages foam cells formation and atherogenesis. There have been insulficient tests of the protective effects of flavonoids against LDL oxidation to make definitive statements about their structure activity relationships. How-ever hydroxylation of the flavone uncleas can appears to be advantageous because polyhydroxylated aglycone flavonoids are potent inhibitor of LDL modification. This identification may lead to new and more effective antioxidant strategies for abrogating the atherosclerotic process the leading cause of death and disability in industrialized societies.

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Molecular Cloning and Characterization of Alkaliphilic Phospholipase B (VFP58) from Vibrio fluvialis

  • AHN SUN HEE;JEONG SEUNG HA;KIM JIN MAN;KIM YOUNG OK;LEE SANG JUN;KONG IN SOO
    • Journal of Microbiology and Biotechnology
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    • v.15 no.2
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    • pp.354-361
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    • 2005
  • Vibrio fluvialis, an enteropathogenic bacterium, produces a phospholipase which is thought to be an important factor in the pathogenesis of disease. In this study, the phospholipase gene (vfp) was identified from V fluvialis (KCTC 2473) and its sequence was determined. The entire open reading frame was composed of 1,689 nuc1eotides and 563 amino acids. The phospholipase gene (vfp) was overexpressed in Escherichia coli as a his-tag fused protein. This recombinant protein (rVFP58) was solubilized with 6 M urea and purified by Ni-NTA affinity chromatography. The action mode of rVFP58 was determined by TLC and GC-MS, and it showed phospholipase B activity, which had both phospholipase A and lysophospholipase activities. The rVFP58 showed a maximum activity at pH around 9- 10 and temperature of about 40OC, and it was stable under alkaline condition over pH 9. The cytotoxicity of rVFP58 was evaluated, using a fish cell line, CHSE-2l4, and was found to cause significant cell death after 14 h of exposure to 250 $\mu$g of the protein.

Signal transfduction pathways for infection structure formation in the rice blast fungus, Magnaporthe grisea

  • Lee, Yong-Hwan;Khang, Chang-Hyun
    • Proceedings of the Botanical Society of Korea Conference
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    • 1999.07a
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    • pp.41-44
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    • 1999
  • Magnaporthe grisea (Hebert) Barr (anamorph: Pyricularia grisea) is a typical heterothallic Ascomycete and the causal agent of rice blast, one of the most destructive diseases on rice (Oryza sativa L.) worldwide. The interactions between cells of the pathogen and those of the host involve a complex of biological influences which can lead to blast disease. The early stages of infection process in particular may be viewed as a sequence of discrete and critical events. These include conidial attachment, gemination, and the formation of an appressorium, a dome-shaped and melanized infection structure. Disruption of this process at any point will result in failure of the pathogen to colonize host tissues. This may offer a new avenue for developing innovative crop protection strategies. To recognize and capture such opportunities, understanding the very bases of the pathogenesis at the cellular and molecular level is prerequisite. Much has been learned about environmental cues and endogenous signaling systems for the early infection-related morphogenesis in M. grisea during last several years. The study of signal transduction system in phytopathogenic filamentous fungi offers distinct advantages over traditional mammalian systems. Mammalian systems often contain multiple copies of important genes active in the same tissue under the same physiological processes. Functional redundancy, alternate gene splicing, and specilized isoforms make defining the role of any single gene difficult. Fungi and animals are closely related kingdoms [3], so inferences between these organisms are often justified. For many genes, fungi frequently possess only a single copy, thus phenotype can be attributed directly to the mutation or deletion of any particular gene of interest.

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북한산 국립공원의 식물상

  • 이영노
    • Proceedings of the Botanical Society of Korea Conference
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    • 1985.08b
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    • pp.19-22
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    • 1985
  • Magnaporthe grisea (Hebert) Barr (anamorph: Pyricularia grisea) is a typical heterothallic Ascomycete and the causal agent of rice blast, one of the most destructive diseases on rice (Oryza sativa L.) worldwide. The interactions between cells of the pathogen and those of the host involve a complex of biological influences which can lead to blast disease. The early stages of infection process in particular may be viewed as a sequence of discrete and critical events. These include conidial attachment, gemination, and the formation of an appressorium, a dome-shaped and melanized infection structure. Disruption of this process at any point will result in failure of the pathogen to colonize host tissues. This may offer a new avenue for developing innovative crop protection strategies. To recognize and capture such opportunities, understanding the very bases of the pathogenesis at the cellular and molecular level is prerequisite. Much has been learned about environmental cues and endogenous signaling systems for the early infection-related morphogenesis in M. grisea during last several years. The study of signal transduction system in phytopathogenic filamentous fungi offers distinct advantages over traditional mammalian systems. Mammalian systems often contain multiple copies of important genes active in the same tissue under the same physiological processes. Functional redundancy, alternate gene splicing, and specilized isoforms make defining the role of any single gene difficult. Fungi and animals are closely related kingdoms [3], so inferences between these organisms are often justified. For many genes, fungi frequently possess only a single copy, thus phenotype can be attributed directly to the mutation or deletion of any particular gene of interest.

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Bioactive Marine Natural Products in Drug Development

  • Kim, Se-Kwon;Ravichandran, Y. Dominic;Kim, Moon-Moo;Jung, Won-Kyo
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.4
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    • pp.209-223
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    • 2007
  • Nature is one of the most important sources of pharmacologically active compounds in the search for drugs against life threatening diseases. Even though plants and terrestrial microorganisms have played as an important source for the new drug candidates from nature, marine organisms such as tunicates, sponges, soft corals, sea horses, sea snakes, marine mollusks, seaweeds, nudibranches, sea slugs and marine microorganisms are increasingly attracting attention in recent years. Marine organisms also have the potential to develop into future drugs against important diseases, such as cancer, a range of bacterial and viral diseases, malaria, and inflammations. Even though the mechanism of action in the molecular level of most metabolites is still unclear, the mechanisms by which they interfere with the pathogenesis of a wide range of diseases have been reported. The knowledge of this is one of the key factors necessary to develop bioactive compounds into medicines. This is due to their structurally unique and pharmacologically active compounds. The potential pharmaceutical, medicinal and research applications of some of these compounds are discussed in hundreds of scientific papers, and are reviewed here.

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Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

  • Yoo, Eun-Sun
    • Clinical and Experimental Pediatrics
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    • v.54 no.3
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    • pp.95-105
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    • 2011
  • Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

NCAM as a cystogenesis marker gene of PKD2 overexpression

  • Yoo, Kyung-Hyun;Lee, Tae-Young;Yang, Moon-Hee;Park, Eun-Young;Yook, Yeon-Joo;Lee, Hyo-Soo;Park, Jong-Hoon
    • BMB Reports
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    • v.41 no.8
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    • pp.593-596
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    • 2008
  • ADPKD (Autosomal Dominant Polycystic Kidney Disease) is characterized by the progressive expansion of multiple cystic lesions in the kidneys. ADPKD is caused by mutations in Ed-pl. consider PKD1 and PKD2. Recently a relation between c-myc and the pathogenesis of ADPKD was reported. In addition, c-Myc is a downstream effector of PKD1. To identify the gene regulated by PKD2 and c-Myc, we performed gene expression profiling in PKD2 and c-Myc overexpressing cells using a human 8K cDNA microarray. NCAM (neuronal cell adhesion molecule) levels were significantly reduced in PKD2 overexpressing systems in vitro and in vivo. These results suggest that NCAM is an important molecule in the cystogenesis induced by PKD2 overexpession.

Oxidative modification of human ceruloplasmin induced by a catechol neurotoxin, salsolinol

  • Kim, Seung-Sub;Kang, Jae Yoon;Kang, Jung Hoon
    • BMB Reports
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    • v.49 no.1
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    • pp.45-50
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    • 2016
  • Salsolinol (SAL), a compound derived from dopamine metabolism, is the most probable neurotoxin involved in the pathogenesis of Parkinson's disease (PD). In this study, we investigated the modification and inactivation of human ceruloplasmin (hCP) induced by SAL. Incubation of hCP with SAL increased the protein aggregation and enzyme inactivation in a dose-dependent manner. Reactive oxygen species scavengers and copper chelators inhibited the SAL-mediated hCP modification and inactivation. The formation of dityrosine was detected in SAL-mediated hCP aggregates. Amino acid analysis post the exposure of hCP to SAL revealed that aspartate, histidine, lysine, threonine and tyrosine residues were particularly sensitive. Since hCP is a major copper transport protein, oxidative damage of hCP by SAL may induce perturbation of the copper transport system, which subsequently leads to deleterious conditions in cells. This study of the mechanism by which ceruloplasmin is modified by salsolinol may provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD. [BMB Reports 2016; 49(1): 45-50]

Cytosolic phospholipase A2, lipoxygenase metabolites, and reactive oxygen species

  • Kim, Cheol-Min;Kim, Joo-Young;Kim, Jae-Hong
    • BMB Reports
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    • v.41 no.8
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    • pp.555-559
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    • 2008
  • Reactive oxygen species (ROS) are generated in mammalian cells via both enzymatic and non-enzymatic mechanisms. Although certain ROS production pathways are required for the performance of specific physiological functions, excessive ROS generation is harmful, and has been implicated in the pathogenesis of a number of diseases. Among the ROS-producing enzymes, NADPH oxidase is widely distributed among mammalian cells, and is a crucial source of ROS for physiological and pathological processes. Reactive oxygen species are also generated by arachidonic acid (AA) metabolites, which are released from membrane phospholipids via the activity of cytosolic phospholipase $A_2$ ($cPLA_2$). In this study, we describe recent studies concerning the generation of ROS by AA metabolites. In particular, we have focused on the manner in which AA metabolism via lipoxygenase (LOX) and LOX metabolites contributes to ROS generation. By elucidating the signaling mechanisms that link LOX and LOX metabolites to ROS, we hope to shed light on the variety of physiological and pathological mechanisms associated with LOX metabolism.