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151.
Cho JY Kim AR Joo HG Kim BH Rhee MH Yoo ES Katz DR Chain BM Jung JH 《Biochemical and biophysical research communications》2004,313(4):954-961
Cynaropicrin is a sesquiterpene lactone displaying immunomodulatory effects on the production of cytokine and nitric oxide from macrophages/monocytes. In this study we have examined inhibitory effect of cynaropicrin on activation of major adhesion molecules [CD29 (beta1 integrins), CD43, and CD98] on the cells assessed by U937 (promonocytic cells) homotypic aggregation. Cynaropicrin potently blocked CD29 (beta1 integrins)- and CD98-induced homotypic aggregation with IC(50) values of 3.46 and 2.98 microM, respectively, without displaying cytotoxicity. Similarly, flow cytometric analysis exhibited that cynaropicrin down-regulated strikingly surface level of CD29 and CD147, a functional regulator of CD98, but not CD43. More importantly, cynaropicrin inhibition was linked to blockade of extracellular signal-related kinase (ERK) activation and distinct from other enzyme inhibitors including rottlerin, propranolol, forskolin, and chloroquine, but not cytochalasin B. Therefore, our finding is the first demonstration that cynaropicrin may be a potent functional regulator of CD29 and CD98 via interrupting ERK activation which may be linked to cytoskeleton rearrangement, suggesting further application to CD29- and CD98-mediated diseases such as virus-induced chronic inflammation, and invasion, migration, and metastasis of leukocyte cancer cells. 相似文献
152.
The effect of long-term treatment with erythromycin on Th1 and Th2 cytokines in diffuse panbronchiolitis 总被引:4,自引:0,他引:4
Park SJ Lee YC Rhee YK Lee HB 《Biochemical and biophysical research communications》2004,324(1):114-117
Diffuse panbronchiolitis (DPB) is a chronic progressive disease of the respiratory bronchioles, and has been improved by low-dose, long-term erythromycin (EMC) treatment. The therapeutic benefits may be derived from its anti-inflammatory and immunomodulatory properties rather than antimicrobial effect. However, there are few studies about the mechanism of immunomodulation by EMC treatment for patient with DPB. In this study, we quantified the changes of Th1 and Th2 cytokines in the bronchoalveolar lavage (BAL) fluid from patients with DPB after long term treatment with EMC. After the EMC treatment, a significant reduction in the number of lymphocytes was observed, and the CD4/CD8 ratio was elevated as well. The IL-2 and IFN-gamma levels in the BAL fluid were significantly decreased and the IL-4, IL-5, and IL-13 levels were significantly increased after EMC treatment. Our results suggest that the therapeutic benefits of long-term EMC treatment may be partially due to the immune system's shift from Th1 to Th2 cytokine production. 相似文献
153.
Sorin EJ Nakatani BJ Rhee YM Jayachandran G Vishal V Pande VS 《Journal of molecular biology》2004,337(4):789-797
Recent studies in protein folding suggest that native state topology plays a dominant role in determining the folding mechanism, yet an analogous statement has not been made for RNA, most likely due to the strong coupling between the ionic environment and conformational energetics that make RNA folding more complex than protein folding. Applying a distributed computing architecture to sample nearly 5000 complete tRNA folding events using a minimalist, atomistic model, we have characterized the role of native topology in tRNA folding dynamics: the simulated bulk folding behavior predicts well the experimentally observed folding mechanism. In contrast, single-molecule folding events display multiple discrete folding transitions and compose a largely diverse, heterogeneous dynamic ensemble. This both supports an emerging view of heterogeneous folding dynamics at the microscopic level and highlights the need for single-molecule experiments and both single-molecule and bulk simulations in interpreting bulk experimental measurements. 相似文献
154.
Hyunmin Song Sei-Ryang Oh Hyeong-Kyu Lee Gyoonhee Han Joo-Heon Kim Hyeun Wook Chang Kyung-Eun Doh Hee-Kyung Rhee Hea-Young Park Choo 《Bioorganic & medicinal chemistry》2010,18(21):7580-7585
5-Lipoxygenase (5-LOX) is important enzyme in the biosynthesis of leukotrienes, and is a potential target in the treatment of asthma and allergy. We designed and synthesized a series of benzoxazoles and benzothiazoles as 5-LOX inhibitors. Fourteen compounds prepared showed the inhibition of LTC4 formation with IC50 value of 0.12–23.88 μM. Also two compounds 2d and 2g showed improved airway hypersensitiveness. 相似文献
155.
Yoo Lim Kam Hee-Kyung Rhee Hwa-Jung Kim Seung Keun Back Heung Sik Na Hea-Young Park Choo 《Bioorganic & medicinal chemistry》2010,18(6):2327-2336
A series of novel non-peptide diamide compounds was synthesized and evaluated as antibradykinin agents by utilizing guinea-pig ileum smooth muscle. Among the final compounds, (Z)-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-4-oxo-N-(4-phenylbutan-2-yl)but-2-enamide showed most favorable bradykinin inhibitory activity and demonstrated analgesic efficacies in the rat models of inflammatory and neuropathic pain. 相似文献
156.
Hydrogen peroxide (H2O2) is an incompletely reduced metabolite of oxygen that has a diverse array of physiological and pathological effects within
living cells depending on the extent, timing, and location of its production. Characterization of the cellular functions of
H2O2 requires measurement of its concentration selectively in the presence of other oxygen metabolites and with spatial and temporal
fidelity in live cells. For the measurement of H2O2 in biological fluids, several sensitive methods based on horseradish peroxidase and artificial substrates (such as Amplex
Red and 3,5,3’5’-tetramethylbenzidine) or on ferrous oxidation in the presence of xylenol orange (FOX) have been developed.
For measurement of intracellular H2O2, methods based on dihydro compounds such as 2’,7’-dichlorodihydrofluorescein that fluoresce on oxidation are used widely
because of their sensitivity and simplicity. However, such probes react with a variety of cellular oxidants including nitric
oxide, peroxynitrite, and hypochloride in addition to H2O2. Deprotection reaction-based probes (PG1 and PC1) that fluoresce on H2O2-specific removal of a boronate group rather than on nonspecific oxidation have recently been developed for selective measurement
of H2O2 in cells. Furthermore, a new class of organelle-targetable fluorescent probes has been devised by joining PG1 to a substrate
of SNAP-tag. Given that SNAP-tag can be genetically targeted to various subcellular organelles, localized accumulation of
H2O2 can be monitored with the use of SNAP-tag bioconjugation chemistry. However, given that both dihydro- and deprotection-based
probes react irreversibly with H2O2, they cannot be used to monitor transient changes in H2O2 concentration. This drawback has been overcome with the development of redox-sensitive green fluorescent protein (roGFP)
probes, which are prepared by the introduction of two redox-sensitive cysteine residues into green fluorescent protein; the
oxidation of these residues to form a disulfide results in a conformational change of the protein and altered fluorogenic
properties. Such genetically encoded probes react reversibly with H2O2 and can be targeted to various compartments of the cell, but they are not selective for H2O2 because disulfide formation in roGFP is promoted by various cellular oxidants. A new type of H2O2-selective, genetically encoded, and reversible fluorescent probe, named HyPer, was recently prepared by insertion of a circularly
permuted yellow fluorescent protein (cpYFP) into the bacterial peroxide sensor protein OxyR. 相似文献
157.
158.
In this study, we adopted a model of tenderness classification in order to determine the factors affecting the tenderness and tenderization characteristics of beef longissimus, using cluster analysis on the basis of Warner-Bratzler shear force and myofibril fragmentation index, at 1, 7, and 14 d. The rate of tenderization was effectively differentiated by pH, R-values, mu-calpain activity, and calpastatin activity. Differences among tenderness classes were generally detected at 3 and 9 h postmortem for metabolic rate, and at 9 and 24 h for the activities of mu-calpain and calpastatin. Early postmortem metabolic rate and calpain system activities were verified as important factors with regard to longissimus tenderization. 相似文献
159.
Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells 总被引:4,自引:0,他引:4
Koon HW Zhao D Zhan Y Rhee SH Moyer MP Pothoulakis C 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):5050-5059
Substance P (SP) via its neurokinin-1 receptor (NK-1R) regulates several gastrointestinal functions. We previously reported that NK-1R-mediated chloride secretion in the colon involves formation of PG. PGE2 biosynthesis is controlled by cyclooxygenase-1 (COX-1) and COX-2, whose induction involves the STATs. In this study, we examined whether SP stimulates PGE2 production and COX-2 expression in human nontransformed NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) and identified the pathways involved in this response. SP exposure time and dose dependently induced an early (1-min) phosphorylation of JAK2, STAT3, and STAT5, followed by COX-2 expression and PGE2 production by 2 h. Pharmacologic experiments showed that PGE2 production is dependent on newly synthesized COX-2, but COX-1 protein. Inhibition of protein kinase Ctheta (PKCtheta), but not PKCepsilon and PKCdelta, significantly reduced SP-induced COX-2 up-regulation, and JAK2, STAT3, and STAT5 phosphorylation. Pharmacological blockade of JAK inhibited SP-induced JAK2, STAT3, and STAT5 phosphorylation; COX-2 expression; and PGE2 production. Transient transfection with JAK2 short-interferring RNA reduced COX-2 promoter activity and JAK2 phosphorylation, while RNA interference of STAT isoforms showed that STAT5 predominantly mediates SP-induced COX-2 promoter activity. Site-directed mutation of STAT binding sites on the COX-2 promoter completely abolished COX-2 promoter activity. Lastly, COX-2 expression was elevated in colon of mice during experimental colitis, and this effect was normalized by administration of the NK-1R antagonist CJ-12,255. Our results demonstrate that SP stimulates COX-2 expression and PGE2 production in human colonocytes via activation of the JAK2-STAT3/5 pathway. 相似文献
160.
Chang-Soo Lee Sang-Ho Lee Yun-Gon Kim Min-Kyu Oh Taek-Sung Hwang Young Woo Rhee Hwan-Moon Song Bo-Yeol Kim Yong-Kweon Kim Byung-Gee Kim 《Biotechnology and Bioprocess Engineering》2006,11(5):455-461
In this study, we have described a method for the fabrication of a protein chip on silicon substrate using hydrophobic thin
film and microfluidic channels, for the simultaneous detection of multiple targets in samples. The use of hydrophobic thin
film provides for a physical, chemical, and biological barrier for protein patterning. The microfluidic channels create four
protein patterned strips on the silicon surfaces with a high signal-to-noise ratio. The feasibility of the protein chips was
determined in order to discriminate between each protein interaction in a mixture sample that included biotin, ovalbumin,
hepatitis B antigen. In the fabrication of the multiplexed assay system, the utilization of the hydrophobic thin film and
the microfluidic networks constitutes a more convenient method for the development of biosensors or biochips. This technique
may be applicable to the simultaneous evaluation of multiple protein-protein interactions. 相似文献