• 동의생리병리학회지
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• 제34권6호
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• pp.326-333
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• 2020

Nitrate-nitrite-nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO2- on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO2 solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO2 diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO2 solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO2-. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO2- caused significantly the production of NO in the cortical tissue but NaNO2 solution with 500ppm of NO2- did not. In summary, these results suggested that F. garlic with high content of NO2- induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

• BMB Reports
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• 제51권4호
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• pp.188-193
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• 2018

Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-${\kappa}B$/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration.

• 융합정보논문지
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• 제10권3호
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• pp.76-91
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• 2020

최근에 한국 고유종인 미선나무 (Abeliophyllum distichum Nakai; Oleaceae) 품종 옥황1호의 유전체가 성공적으로 해독되었다. Acteoside는 다양한 활성을 가지는 물질이며, 여러개의 생화학합성과정이 제시되어왔고, 이들을 통합 검토하여 정확한 생화학합성과정을 완성하였다. 유전체 데이터로부터 2차대사산물을 예측할 수 있는 MetaPre-AI^TM와 정확한 acteoside 생화학합성과정, InfoBoss Pathway Database를 활용하여, acteoside에 관여하는 모든 효소의 유전자를 옥황1호 유전체로부터 성공적으로 확인하였다. 이는 옥황1호는 acteoside 물질을 생산할 수 있는 가능성이 있음을 의미한다. 이에 고성능액체크로마토그래피를 사용하여 옥황1호의 캘러스 세포를 분석하여 acteoside과 이의 유도체인 isoacteoside를 확인하였다. 본 연구는 MetaPre-AI^TM은 유전체로부터 2차대사산물을 성공적으로 예측하였다. 이 방법은 화학물질보다 안정적인 DNA를 분석하여 2차 대사산물을 예측하는 효율적인 방법이 될 것이다.

• 식물조직배양학회지
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• 제24권4호
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• pp.233-238
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• 1997

Salicylic acid (SA) is involved in the establishment of systemic acquired resistance (SAR) in many plant including tobacco. Considering the important role of SA in disease resistance, biosynthetic and metabolic pathways of SA in tobacco have been studied extensively: The initial step for biosynthetic pathway of SA is conversion of phenylalanine to trans-cinnamic acid, followed by decarboxylation of trans-cinnamic acid to benzoic acid and ie subsequent ring hydroxylation at the C-2 position to form SA. In TMV inoculated tobacco, most of the newly synthesized SA is glucosylated or methylated. Methyl salicylate has been identified as a biologically active, volatile signal. In contrast, the two glucosylated forms accumulate in the vicinity of lesions and consist of SA glucoside, a major metabolite, and SA glucose ester, a relatively minor from. Two enzymes involved in SA biosynthesis and metabolism have been purified and characterized : benzoic acid 2-hydroxylase which catalyzes conversion of benzoic acid to SA; UDP-Glucose: SA 1-O-D glucosyltransferase which converts SA to SA glucose ester. Further studies of the biosynthetic and metabolic pathways of SA will help to elucidate the SAR signal transduction pathway and provide potential tools for the manipulation of disease resistance.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2002년도 추계학술대회
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• pp.27-30
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• 2002

Ralstonia eutrupha JMP134 is a well-known soil bacterium which can metabolite diverse aromatic compounds and xenobiotics, such as phenol, 2,4-dichlorophenoxy acetic acid (2, 4-D), and trichloroethylene (TCE), etc. Phenol is degraded through chromosomally encoded phenol degradation pathway. Phenol is first metabolized into catechol by a multicomponent phenol hydroxylase, which is further metabolized to TCA cycle intermediates via a meta-cleavage pathway. The nucleotide sequences of the genes for the phenol hydroxylase have previously been determined, and found to composed of eight genes phlKLMNOPRX in an operon structure. The phlR, whose gene product is a NtrC-like transcriptional activator, was found to be located at the internal region of the structural genes, which is not the case in most bacteria where the regulatory genes lie near the structural genes. In addition to this regulatory gene, we found other regulatory genes, the phlA and phlR2, downstream of the phlX. These genes were found to be overlapped and hence likely to be co-transcribed. The protein similarity analysis has revealed that the PhlA belongs to the GntR family, which are known to be negative regulators, whereas the PhlR2 shares high homology with the NtrC-type family of transcriptional activators like the PhlR. Disruption of the phlA by insertional mutation has led to the constitutive expression of the activity of phenol hydroxylase in JMP134, indicating that PhlA is a negative regulator. Possible regulatory mechanisms of phenol metabolism in R. eutropha JMP134 has been discussed.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권4호
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• pp.219-226
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• 2000

The application of recombinant DNA technology to restructure metabolic net-work can change metabolite and protein products by altering the biosynthetic pathways in an organism. Although some success has been achieved, a more detailed and thorough investigation of this approach is certainly warranted since it is clear that such methods hold great potential based on the encouraging results obtained so far. In last decade, there have been tremendous advances in the field of glycobiology and the stage has been set for the biotechnological production of glycoproteins for therapeutic use. Today glycoproteins are one of the most important groups of pharmaceutical products. In this study the attempt was made to focus on identifying technologies that may have general application for modifying glycosylation pathway of the yeast cells in order to produce glycoproteins of therapeutic use. The carbohydrates of therapeutic recombinant glycoproteins play very important roles in determining their pharmacokinetic properties. A number of biological interactions and biological functions mediated by glycans are also being targeted for therapeutic manipulation in vivo. For a commercially viable production of therapeutic glycoproteins a metabolic engineering of a host cell is yet to be established.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.765-774
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• 2021

Although research on the osteal signaling pathway has progressed, understanding of gut microbial-dependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2001년도 추계학술대회
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• pp.157-163
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• 2001

Mycolic acid-containing gram-positive bacteria, so called nocardioform actinomycetes, have become a great interest to environmental microbiologists due to their metabolic versatility, multidegradative capacity and potential for bioremediation of priority pollutants. For example, Rhodococcus rhodochrous N75 was able to metabolize 4-methy1catechol via a modified $\beta$-ketoadipate pathway whereby 4-methylmuconolactone methyl isomerase catalyzes the conversion of 4-methylmuconolactone to 3-methylmuconolactone in order to circumvent the accumulation of the 'dead-end' metabolite, 4-methylmuconolactone. R. rhodochrous N75 has also shown the ability to transform a range of alkyl-substituted catechols to the corresponding muconolactones. A novel 3-methylmuconolactone-CoAsynthetase was found to be involved in the degradation of 3-methylmuconolactone, which is not mediated in a manner analogous to the classical $\beta$-ketoadipate pathway but activated by the addition of CoA prior to hydrolysis of lactone ring, suggesting that the degradative pathway for methylaromatic compounds by gram-positive bacteria diverges from that of proteobacteria. Mycobacterium sp. Strain PYR-l isolated from oil-contaminated soil was capable of mineralizing various polyaromatic hydrocarbons (PAHs), such as naphthalene, phenanthrene, pyrene, fluoranthrene, 1-nitropyrene, and 6-nitrochrysene. The pathways for degradation of PAHs by this organism have been elucidated through the isolation and characterization of chemical intermediates. 2-D gel electrophoresis of PAH-induced proteins enabled the cloning of the dioxygenase system containing a dehydrogenase, the dioxygenase small ($\beta$)-subunit, and the dioxygenase large ($\alpha$)-subunit. Phylogenetic analysis showed that the large a subunit did not cluster with most of the known sequences except for three newly described a subunits of dioxygenases from Rhodococcus spp. and Nocardioides spp. 2-D gel analysis also showed that catalase-peroxidase, which was induced with pyrene, plays a role in the PAH metabolism. The survival and performance of these bacteria raised the possibility that they can be excellent candidates for bioremediation purposes.

• 한국미생물·생명공학회지
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• 제34권1호
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• pp.35-39
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• 2006

높은 C4 대사활성을 보이는 반추위미생물이 가지는 포도당 발효대사 조절양식의 한가지를 대장균에서 모사하였다. 대장균은 glycolytic condition에서는 phosphoenolpyruvate(PEP) ${\leftrightarrow}$ oxaloacetate(OAA)간 반응을 phosphenolpyruvate carboxylase(PPC)에 의해, gluconeogenetic condition에서는 phosphoenolpyruvate carboxykinase(PCK)에 의해 촉매하도록 조절한다. 반면 반추위미생물은 glycolytic condition에서 PCK를 통하여 반응이 촉매된다. 이러한 조절양식의 차이점이 C4 대사활성에 미치는 영향을 조사하기 위하며 ppc가 돌연변이되고 대신 인위적으로 PCK를 발현할 수 있는 대장균을 제조하였다. 이렇게 PEP-OAA간 대사조절이 변이된 대장균 K12 ppc-/pck+는 야생형 K12보다 2.5배의 높은 C4대사활성을 보였다. 대장균에서의 C4 대사생리를 증가시키는 연구는 대사공학을 이용한 여러가지 유용물질(i.e. 숙신산, ALA)생산에 응용하기 위한 기초자료로 활용될 수 있을 것으로 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권5호
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• pp.547-554
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• 2017

Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon $(IFN)-{\beta}$ mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF) and TANK-binding kinase 1 (TBK1). A mechanism study revealed that HQ inhibited IRF-3 phosphorylation induced by lipopolysaccharide (LPS), TRIF, and AKT by suppressing phosphorylation of AKT, an upstream kinase of the IRF-3 signaling pathway. IRF-3 phosphorylation is highly induced by wild-type AKT and poorly induced by an AKT mutant, AKT C310A, which is mutated at an inhibitory target site of HQ. We also showed that HQ inhibited IRF-3 phosphorylation by targeting all three AKT isoforms (AKT1, AKT2, and AKT3) in RAW264.7 cells and suppressed IRF-3-mediated luciferase activities induced by AKT in HEK293 cells. Taken together, these results strongly suggest that HQ inhibits the production of a type I IFN, $IFN-{\beta}$, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.