• Journal of Microbiology and Biotechnology
• /
• v.16 no.3
• /
• pp.391-398
• /
• 2006

$NF-{\kappa}B$ is a transcription factor involved in the innate immunity against bacterial infection and inflammation. It is also known to render cells resistant to the apoptosis caused by some anticancer drugs. Such a chemoresistance of cancer cells may be related to the activation of $NF-{\kappa}B$ transcription factor; however, the mechanism of activation is not well understood. Here, we demonstrate that a chemotherapeutic agent, etoposide, independently stimulates the $I{\kappa}B{\alpha}$ degradation pathway and PI3-kinase/Akt signaling pathway: The classical $I{\kappa}B{\alpha}$ degradation pathway leads to the nuclear translocation and DNA binding of p65 subunit through $IKK{\beta}$ kinase, whereas the PI3-kinase/Akt pathway plays a distinct role in activating this transcription factor. The PI3-kinase/Akt pathway acts on the p50 subunit of the $NF-{\kappa}B$ transcription factor and enhances the DNA binding affinity of the p50 protein. It may also explain the role of the PI3-kinase/Akt pathway in the anti-apoptotic function of $NF-{\kappa}B$ during chemoresistance of cancer cells.

• Journal of Microbiology and Biotechnology
• /
• v.8 no.2
• /
• pp.146-151
• /
• 1998

The aminoglycoside multiple-resistance determinant from Streptoalloteichus hindustanus was cloned into Streptomyces lividans and named nbrB. The 1.2-kb ApaI- BclI fragment encompassing nbrB was located within a 2.6-kb ApaI fragment by successive subcloning experiments. The complete DNA nucleotide sequence of 1.2-kb containing nbrB was determined. The sequence contains an open reading frame that putatively encodes a polypeptide of 281 amino acids with a predicted molecular weight of 30,992. The deduced amino acid sequence of nbrB shows identities of 85.1% to kgmB of S. tenebrarius, 59.6% to sgm of Micromonospora zionensis, and 57.7% to grm of M. rosea. The similarity of nbrB to kgmB suggests that nbrB encodes a 16S rRNA methylase similar to that encoded by kgmB and that both genes might be derived from a common ancestral gene.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.05b
• /
• pp.88.2-98
• /
• 2002

A wide arry of naturally occurring substances particularly those present in dietary and medicinal plants, have been reported to possess substantial cancer chemopreventive properties. Certain phytochemicals retain strong antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activities. Inducible cyclooxygenase(COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. There is some evidence that expression of both COX-2 and iNOS is co-regulated by the eukaryotic transcription factor NF-$textsc{k}$B. Increased expression of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory diseases. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activies are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. An example is curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), that strongly occurring diaryl heptanoids structurally related to curcumin have substantial anti-tumor promotional activities in two-stage mouse skin carcinogenesis. Thus, yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3heptanone] and yakuchinone B [1-(4'-hydroxy-3'methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberacease) attenuate phorbol ester-induced inflammation and papilloma formation in female ICR mice. These diarylheptanoids also suppressed phorbol ester-induced activation of epdermal ornithine decarboxylase and its mRNA expression when applied onto shaven backs of mice. Yakuchinone A and B as well as curcumin inhibited phorbol ester-induced expression of COX-2 and iNOS and their mRNA in mouse skin via inactivation of NF-$textsc{k}$B. Capsaicin, a major pungent ingredient of red pepper also attenuated phorbol ester-induced NF-$textsc{k}$B activation. Similar suppression of COX-2 and iNOS and down-regulation of NF-$textsc{k}$B activation for its DNA binding were observed with the ginsenosied Rg3 and the ethanol extract of Artemisia asiatica. We have also found that certain anti-inflammatory phytochemicals exert inhibitory effects on phorbol ester-induced COX-2 expression and NF-$textsc{k}$B activation in immortalized human breast epithelial (MCF-10A) cells in culture. One of the plausible mechanisms undelying inhibition by aforementioned phytochemicals of phorbol ester-induced NF-$textsc{k}$B activation involves interference with degragation of the inhibitory unit, I$textsc{k}$Ba, which blocks subsequent nuclear translocation of the functionally active p65 subunit of NF-$textsc{k}$B. the activation of epidermal NF-$textsc{k}$B by phorbol ester and subsequent induction of COX-2 hence appear to play an important role in intracellular signaling pathwasy leading to tumor promotion and targeted inhibition of NF-$textsc{k}$B may provide a new promising cancer chemopreventive strategy.

• Applied Biological Chemistry
• /
• v.33 no.3
• /
• pp.231-238
• /
• 1990

The structure-antifungal activity correlations between the structure of fourteen new 1-(phenoxymethyl)benzotriazoles (I) (Y=0), 1-(thiophenoxymethyl)benzotriazoles (ll) (Y=S) and 1-(azidomethyl)benzotriazole (III) derivatives were synthesized, and their activity, fifty percent inhibition of mycelial growth($pI_{50}$), in vitro against Pyricularia oryzae, Fusarium axysporum f.sp sesami, Valsa ceratosperma and Botrytis cinerea were investigated using a generalized QSAR method. The activity of (I) was superior In those of (II) and (III). The effect of the substituents (X) on the phenoxy group (I) was rationalized by a parabolic function of electronic (${\sigma}$), steric ($B_1$) and hydrophobic parameter(${\pi}$), and hydrogen bonding (HB). Where the optimal values of substituent on the fungicidal activity againt P. oryzae and F. axysporum f.sp.sesami are $B_1=1.40A;(H)$ and ${\pi}=0.07{\sim}0.15;(H)$, and those of substituent on the fungicidal activity against V. ceratosperma and B. cinerea are ${\sigma}=0.23{\sim}0.28;\;(C1),\;{\pi}=0.70;$ (C1), respectively. The most effective compound ( I a) and ( I d) were examined in this study.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.5
• /
• pp.551-562
• /
• 2003

Background : NF-${\kappa}B$ is a characteristic transcriptional factor which has been shown to regulate production of acute inflammatory mediators and to be involved in the pathogenesis of many inflammatory lung diseases. There has been some evidence that PI3K/Akt pathway could activate NF-${\kappa}B$ in human cell lines. However, the effect of PI3K/Akt pathway on the activation of NF-${\kappa}B$ varied depending on the cell lines used in the experiments. In this study we evaluated the effect of PI3K/Akt pathway on the activation of NF-${\kappa}B$ in human respiratory epithelial cell lines. Methods : BEAS-2B, A549 and NCI-H157 cell lines were used in this experiment. To evaluate the activation of Akt activation and I${\kappa}B$ degradation, cells were analysed by western blot assay using phospho-specific Akt Ab and $I{\kappa}B$ Ab. To block PI3K/Akt pathway, cells were pretreated with wortmannin or LY294002 and transfected with dominant negative Akt (DN-Akt). For IKK activity, immune complex kinase assay was performed. To evaluate the DNA binding affinity and transcriptional activity of NF-${\kappa}B$, electrophoretic mobility shift assay (EMSA) and luciferase assay were performed, respectively. Results : In BEAS-2B, A549 and NCI-H157 cell lines, Akt was activated by TNF-$\alpha$ and insulin. Activation of Akt by insulin did not induce $I{\kappa}B{\alpha}$ degradation. Blocking of PI3K/Akt pathway via wortmannin/LY294002 or DN-Akt did not inhibit TNF-$\alpha$-induced $I{\kappa}B{\alpha}$ degradation or IKK activation. Inhibition of PI3K/Akt did not affect TNF-$\alpha$-induced NF-${\kappa}B$ activation. Overexpression of DN-Akt did not block TNF-$\alpha$-induced transcriptional activation of NF-${\kappa}B$, but wortmannin enhanced TNF-$\alpha$-induced in NF-${\kappa}B$ transcriptional activity. Conclusion : PI3K/Akt was not involved in TNF-$\alpha$-induced $I{\kappa}B{\alpha}$ degradation or transcriptional activity of NF-${\kappa}B$ in human respiratory epithelial cell lines.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.14 no.12
• /
• pp.6542-6549
• /
• 2013

In highly elevated piers and long span beams, a hollow section is often used to reduce the self-weight and increase the flexural rigidity of members. Numerical analysis was conducted to obtain the moment-curvature curves and curvature ductility factor for the RC hollow section beams under a range of hollow portion sizes and reinforcement conditions in the upper flange and web. The curvature ductility factor was constantly maintained until the hollow portion size($b_i/b_o/h_i/h_o$) was less than or equal to 0.5. The curvature ductility factor decreased sharply if ($b_i/b_o/h_i/h_o$) was 0.7 or more. The curvature ductility factor of the beam decreased if reinforcement was provided in the web of the RC hollow section beam. To obtain the same level of the ductility factor as the singly reinforced section, the reinforcement should be provided in the upper flange as much as the web reinforcement.

• Journal of the Korea Institute of Information and Communication Engineering
• /
• v.16 no.5
• /
• pp.1023-1028
• /
• 2012

A MMIC (Monolithic Microwave Integrated Circuit) mixer chip using the Schottky diode of an GaAs p-HEMT process has been developed for the I/Q demodulator of non-contact near field microwave probing system. A single balanced mixer type is adopted to achieve simple structure of the I/Q demodulator. A quadrature hybrid coupler and a quarter wavelength transmission line for 180 degree hybrid are realized with lumped elements of MIM capacitor and spiral inductor to reduce the mixer chip size. According to the on-wafer measurement, this MMIC mixer covers RF and LO frequencies of 1650MHz to 2050MHz with flat conversion loss. The MMIC mixer with miniature size of $2.5mm{\times}1.7mm$ demonstrates conversion loss below 12dB for both variations of RF and LO frequencies, LO-to-IF isolation above 43dB and RF-to-IF isolation above 23dB, respectively.

• Korean Journal of Veterinary Research
• /
• v.51 no.3
• /
• pp.217-225
• /
• 2011

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B ($NF{\kappa}B$) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, $NF{\kappa}B$ activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of $NF{\kappa}B$ activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of $NF{\kappa}B$ and phospho-$I{\kappa}B$ proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of $NF{\kappa}B$ and phospho-$I{\kappa}B$ significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of $NF{\kappa}B$ and phophorylation of $I{\kappa}B$ in the CNS. Subsequently, the inhibition of $NF{\kappa}B$ activation and $I{\kappa}B$ phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.4
• /
• pp.1115-1119
• /
• 2013

A kinetic study is reported for nucleophilic substitution reactions of benzyl 2-pyridyl thionocarbonate (5b) and t-butyl 2-pyridyl thionocarbonate (6b) with a series of alicyclic secondary amines in $H_2O$ at $25.0^{\circ}C$. General-base catalysis, which has often been reported to occur for aminolysis of esters possessing a C=S electrophilic center, is absent for the reactions of 5b and 6b. The Br${\o}$nsted-type plots for the reactions of 5b and 6b are linear with ${\beta}_{nuc}$ = 0.29 and 0.43, respectively, indicating that the reactions of 5b proceed through a stepwise mechanism with formation of a zwitterionic tetrahedral intermediate ($T^{\pm}$) being the rate-determining step while those of 6b proceed through a concerted mechanism. The reactivity of 5b and 6b is similar to that of their oxygen analogues (i.e., benzyl 2-pyridyl carbonate 5a and t-butyl 2-pyridyl carbonate 6a, respectively), indicating that the effect of modification of the electrophilic center from C=O to C=S (i.e., from 5a to 5b and from 6a to 6b) on reactivity is insignificant. In contrast, 6b is much less reactive than 5b, indicating that the replacement of the $PhCH_2$ in 5b by the t-Bu in 6b results in a significant decrease in reactivity as well as a change in the reaction mechanism (i.e., from a stepwise mechanism to a concerted pathway). It has been concluded that the contrasting reactivity and reaction mechanism for the reactions of 5b and 6b are not due to the electronic effects of $PhCH_2$ and t-Bu but are caused by the large steric hindrance exerted by the bulky t-Bu in 6b.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.4
• /
• pp.239-246
• /
• 2003

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation and can be inhibited with sodium salicylate. $TNF-{\alpha}$ plus $IFN-{\gamma}$ can induce extracellular signal-regulated kinase (ERK), IKK, $I{\kappa}B$ degradation and NF-${\kappa}B$ activation. The inhibition of the ERK pathway with selective inhibitor, PD098059, blocked cytokine-induced COX-2 expression and $PGE_2$ release. Salicylate treatment inhibited COX-2 expression induced by $TNF-{\alpha}$/$IFN-{\gamma}$ and regulated the activation of ERK, IKK and $I{\kappa}B$ degradation and subsequent NF-${\kappa}B$ activation in MC3T3E1 osteoblasts. Furthermore, antioxidants such as catalase, N-acetyl-cysteine or reduced glutathione attenuated COX-2 expression in combined cytokines-treated cells, and also inhibited the activation of ERK, IKK and NF-${\kappa}B$ in MC3T3E1 osteoblasts. In addition, $TNF-{\alpha}$/$IFN-{\gamma}$ stimulated ROS release in the osteoblasts. However, salicylate had no obvious effect on ROS release in DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, $I{\kappa}B$ degradation and NF-${\kappa}B$ activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of ERK, IKK, $I{\kappa}B$, $NF-{\kappa}B$ and resultant COX-2 expression pathway.