• 제목/요약/키워드: 2, 3-dioxygenase

검색결과 124건 처리시간 0.023초

Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases

  • Lee, Hong Kyung;Lim, Sang Hee;Chung, In Sung;Park, Yunsoo;Park, Mi Jeong;Kim, Ju Young;Kim, Yong Guk;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • 제14권2호
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    • pp.81-88
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    • 2014
  • Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-${\beta}$, hepatic growth factors, prostaglandin $E_2$, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

Streptomycetes Inducible Gene Cluster Involved in Aromatic Compound Metabolism

  • 박현주;김응수
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2003년도 생물공학의 동향(XII)
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    • pp.422-427
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    • 2003
  • Streptomyces setonii (ATCC 39116) is a Gram-positive thermophilic soil actinomycetes capable of degrading single aromatic compounds including phenol and benzoate via ortho-cleavage pathway. we isolated approximately 6.3-kb S. setonii DNA fragment containing a thermophilic catechol 1,2-dioxygenase(C12O) gene. Here we further revealed that the 6.3-kb S. setonii DNA fragment was organized into two putative divergently-transcribed clusters with 6 complete and one incomplete open reading frames (ORFs). The first cluster with 3 ORFs showed significant homologies to previously known benA, benB, and benC, implying a part of benzoate catabolic operon. The second cluster revealed an ortho-cleavage catechol catabolic operon with three translationally-coupled ORFs (catR, catB, catA). Each of these individually-cloned ORFs was expressed in E. coli and identified as a distinct protein band with a theoretical molecular weight in SDS-PAGE. The expression of the cloned S. setonii catechol operon was induced in a heterologous S. lividans by specific single aromatic compounds including catechol, phenol, and 4-chlorophenol. The simitar induction pattern was also observed using a luciferase gene-fused reporter system, implying that S. setonii employs an inducer-specific regulatory mechanism for aromatic compound metabolism.

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목질리그닌의 생물학적 분해시 백색 부후균류 효소들의 상호작용 (Enzymes of White-rot Fungi Cooperate in Biodeterioration of Lignin Barrier)

  • 안드레 레오노비취;조남석;마리아 바실레브스카;죠오지 로갈스키;올란타 루테랙
    • Journal of the Korean Wood Science and Technology
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    • 제25권2호
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    • pp.1-20
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    • 1997
  • 목재를 분해시키는 담자균류들은 목재 및 목질복합체에 쉽사리 침투하여 복잡한 리그노셀룰로오스 복합체를 분해시킨다. 이러한 분해에는 많은 효소시스템들이 복합적으로 작용하면서 상호 협동하는 것으로 보고되고 있다. 지금까지 일려진 효소들은 통상 3개의 그룹으로 나눌 수 있는데 그 하나는 목재성분을 직접적으로 공격하는 효소균들, 예를 들면 cellulase complex, laccase(LAC), lignin peroxidase(LIP), horse-radish peroxidase(HRP), manganese-independent peroxidase(MIP) 및 protocatechuate 3,4-dioxygenase(PCD) 등이 있고, 두번째 그룹으로서 manganese-dependent peroxidase(MnP), aryl alcohol oxidase(AAO) 및 glyoxal oxidase(GLO) 등인데, 이들 효소들은 목질을 직접적으로 공격하지 않고 제1그룹의 효소들과 협동하여 작용하는 것으로 알려지고 있다. 제3그룹의 효소들은 glucose oxidase(GOD) 및 cellobiose : quinone oxidoreductase(CBQ)로서 feedback type의 효소들로서 목재고분자의 분해시 대사의 고리를 결합시켜 주는 매우 중요한 기능을 하는 효소군들이다. 그러나 이 이외에도 다른 분해기구가 밝혀지고 있으며 기타 효소들에 의한 리그노셀룰로오스의 분해반응기구의 해명에는 상당한 시간이 걸릴 것으로 사료된다.

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사이토카인과 우울증 (Cytokines and Depression)

  • 김용구
    • 생물정신의학
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    • 제15권3호
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    • pp.175-185
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    • 2008
  • Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

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Monitoring Expression of bphC Gene from Ralstonia eutropha H85O Induced by Plant Terpenes in Soil

  • Jung, Kyung-Ja;Kim, Byung-Hyuk;Kim, Eungbin;So, Jae-Seong;Koh, Sung-Cheol
    • Journal of Microbiology
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    • 제40권4호
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    • pp.340-343
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    • 2002
  • A PCB degrader, Ralstonia eutropha H850 was shown to induce bphC gene encoding 2,3-dihydroxy-biphenyl-1,2-dioxygenase in a carvone-amended pure culture in our previous study (Park et al.,1999). The present study was carried out to examine how plant terpenes, as natural substrates, would cause an expression of a PCB degradative gene in soil that was amended with terpenes. The population of Ralstonia eutropha H850 was maintained at least around 10$\^$8/ (CFU/g fresh soil) in the soil amended with carvone or limonene in the presence of succinate as a growth substrate at 50 th day. The gene expression was monitored by RT-PCR using total RNA directly extracted from each soil and bphC gene primers. The bphC gene expression of the seeded strain H850 was observed in the soil amended with biphenyl (4 days) but not with succinate, carvone and limonene. These results indicate that terpenes widely distributed in nature could be a potential inducing substrate for effective PCB biodegration in the soil but their bioavailability and specific induction behavior should be taken into account before PCB bioremediation implementation.

Characterization of the pcbD Gene Encoding 2-Hydroxy-6-Ox0-6-Phenylgexa-2,4-Dienoate Hydrolase from Pseudomonas sp. P20

  • Lim, Jong-Chul;Lee, Jeong-Rai;Lim, Jai-Yun;Min, Kyung-Rak;Kim, Chi-Kyung;Ki, Young-Soo
    • Journal of Microbiology and Biotechnology
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    • 제10권2호
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    • pp.258-263
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    • 2000
  • 2-Hydroxy-6-oxo-6phenylhexa-2,4-dienoate (HOPDA) hydrolase catalyzes the hydrolytic cleavage of HOPDA to bemzpate and 2-hydroxypenta-2, 4-dienoate (HPD) during microbial catabolism of biphenyl and polychlorinated biphenyls. A HOPDA hydrolase gene (pcbD) was isolated from the genomic library of Pseudomonas sp. P20 and designated as pCNUO1201; a 7.5-kb XbaI DNA fragment from Pseudomonas sp. P20 was inserted into the pBluescript SK(+) XbaI site. E. coli HB101 harboring pCNU1201 exhibited HOPDA hydrolase activity. The open reading frame (ORF) corresponding to the pcbD gene consisted of 855 base pairs with an ATG initiation codon and a TGA termination codon. The ORF was preceded by a rebosome-binding sequence of 5'-TGGAGC-3' and its G+C content was 55 mol%. The pcbD gene of Pseudomonas sp. P20 was located immedeately downstream of the pcbC gene encoding 2,3- dihydroxybiphenyl 1,2-dioxygenase, and approximately 4-kb upstream of the pcbE gene encoding HPD hydratase. The pcbK gene was able to encode a polypeptide with a molecular weight of 31,732 containing 284 amino acid residues. The deduced amino acid sequence of the HOPDA hydrolase of Pseudomonas sp. P20 exhibited high identity (62%) with those of the HOPDA hydrolases of P. putida KF715, P. pseudoalcaligenes KF707, and Burkholderia cepacia LB400, and also significant homology with those of other hydrolytic enzymes including esterase, transferase, and peptidase.

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Caffeic acid phenethyl ester protects against photothrombotic cortical ischemic injury in mice

  • Hwang, Sun Ae;Kim, Chi Dae;Lee, Won Suk
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권1호
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    • pp.101-110
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    • 2018
  • In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5-5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult. CAPE significantly reduced the infarct size as well as the expression of tumor necrosis $factor-{\alpha}$, hypoxiainducible $factor-1{\alpha}$ monocyte chemoattractant protein-1, $interleukin-1{\alpha}$, and indoleamine 2,3-dioxygenase in the cerebral cortex ipsilateral to the photothrombosis. Moreover, it induced an increase in heme oxygenase-1 immunoreactivity and interleukin-10 expression. These results suggest that CAPE exerts a remarkable neuroprotective effect on ischemic brain injury via its anti-inflammatory properties, thereby providing a benefit to the therapy of cerebral infarction.

Inhibition of Prolyl 4-Hydroxylase by Oxaproline Tetrapeptides In Vitro and Mass Analysis for the Enzymatic Reaction Products

  • Moon Hong-sik;Begley Tedhg P.
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제5권1호
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    • pp.61-64
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    • 2000
  • A series of 5-oxaproline peptide derivatives was synthesized and evaluated for its ability to inhibit the prolyl 4-hydroxylase in vitro. Structure-activity studies show that the 5-oxaproline sequences, prepared by the 1,3-dipolar cycloaddition of the C-methoxycarbonyl-N-mannosyl nitrone in the presence of the ethylene, are more active than the corresponding proline derivatives. Prolyl 4-hydroxylase belongs to a family of $Fe^{2+}-dependent$ dioxygenase, which catalyzes the formation of 4-hydroxyproline in collagens by the hydroxylation of proline residues in -Gly-Xaa-Pro-Gly- of procollagen chains. In this paper we discover the more selective N-Cbz-Gly-Phe-Pro-Gly-OEt $(K_m\;=\;520\;{\mu}M)$ sequences which are showed stronger binding than others in vitro. Therefore, we set out to investigate constrained tetrapeptide that was designed to mimic the proline structure of pep tides for the development of prolyl 4-hydroxylase inhibitor. From this result, we found that the most potent inhibitor is N-Dansyl-Gly-Phe-5-oxaPro-Gly-OEt $(K_i\;=\;1.6\;{\mu}M)$. This has prompted attempts to develop drugs which inhibit collagen synthesis. Prolyl 4-hydroxylase would seem a particularly suitable target for antifibrotic therapy.

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Regulation of hormone-related genes involved in adventitious root formation in sweetpotato

  • Nie, Hualin;Kim, Sujung;Lee, Yongjae;Park, Hyungjun;Lee, Jeongeun;Kim, Jiseong;Kim, Doyeon;Kim, Sunhyung
    • Journal of Plant Biotechnology
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    • 제47권3호
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    • pp.194-202
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    • 2020
  • The sweetpotatoes (Ipomoea batatas) generate adventitious roots (ARs) from cut stems that develop into storage roots and make for an important means of propagation. However, few studies have investigated the hormones involved in AR development in sweetpotato. In this study, the expression patterns of hormone-related genes involved in AR formation were identified using the transcriptome data. RNA-seq data from stems grown for 0 and 3 days after cutting were analyzed. In addition, hormone-related genes were identified among differentially expressed genes (DEGs) and filtered genes, and cluster analysis was used to characterize expression patterns by function. Most hormone-related regulated genes expressed 3 days after growing the cut stems were abscisic acid (ABA)-related genes, followed by ethylene- and auxin-related genes. For ABA, the biosynthesis genes (including genes annotated to NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3)) and signal transduction and perception genes (including genes annotated to PROTEIN PHOSPHATASE 2Cs (PP2Cs)) tended to decrease. Expression patterns of auxin- and ethylene-related genes differed by function. These results suggest that ABA, auxin, and ethylene genes are involved in AR formation and that they may be regulated in a hormone function-dependent manner. These results contribute to the identification of hormone functions during AR formation and may contribute to understanding the mechanism of AR formation in the sweetpotato.

Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

  • Hui-Won Park;Sun-Hee Park;Hyeon-Ju Jo;Tae-Gyu Kim;Jeong Hyun Lee;Seung-Goo Kang;Young-Saeng Jang;Pyeung-Hyeun Kim
    • IMMUNE NETWORK
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    • 제20권5호
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    • pp.38.1-38.12
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    • 2020
  • Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3+ induced Treg (iTreg) differentiation in ovalbumin-specific CD4+ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.