• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.94-94
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• 2019

In this study, we elucidated the anti-inflammatory mechanisms of leaves extracts from Rodgersia podophylla (RPL) in RAW264.7 cells. RP-L significantly inhibited the production of the proinflammatory mediators such as NO, iNOS, IL-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. RPL increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of RPL against LPS-induced NO production in RAW264.7 cells. Inhibition of p38, ROS and $GSK3{\beta}$ attenuated RPL-mediated HO-1 expression. Inhibition of ROS inhibited p38 phosphorylation and $GSK3{\beta}$ expression induced by RPL. In addition, inhibition of $GSK3{\beta}$ blocked RPL-mediated p38 phosphorylation. RPL induced nuclear accumulation of Nrf2, and Inhibition of p38, ROS and $GSK3{\beta}$ abolished RPL-mediated nuclear accumulation of Nrf2. Furthermore, RPL blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65. RP-L also attenuated LPS-induced phosphorylation of ERK1/2 and p38. Our results suggest that RPL exerts potential antiinflammatory activity by activating ROS/$GSK3{\beta}$/p38/Nrf2/HO-1 signaling and inhibiting NF-${\kappa}B$ and MAPK signaling in RAW264.7 cells. These findings suggest that RPL may have great potential for the development of anti-inflammatory drug.

• Animal cells and systems
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• v.9 no.3
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• pp.173-179
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• 2005

Cyclic-AMP-dependent protein kinase (PKA) seems to function as a negative regulator of the c-Jun $NH_2-terminal$ kinase (JNK) signaling pathway. We demonstrate here that the activity of the PKA catalytic subunit (PKAc) is reduced in apoptotic PC12 pheochromocytoma cells. Apoptotic progress was inhibited by dibutyryl cyclic AMP (dbcAMP), an analog of cAMP. The rescue by dbcAMP was attributable to inhibition of the JNK but not of the p38 signaling pathway, due to the induction of PKA activity. JNK was present in immunocomplexes of PKAc, and PKAc phosphorylated JNK in vitro. Presence of p38 kinase, however, was not prominent in immunocomplexes of PKAc. Our data suggest that JNK is a target point of negative regulation by PKAc in the JNK signaling pathway.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.148.1-148.1
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• 2003

Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. Previously, we have shown that ceramide induces Bax translocation which is associated with cytochrome c release from the mitochondria. In this study, we show that p38 MAP kinase is involved in ceramide-induced Bax translocation. In human leukemic cells, ceramide stimulated the phosphorylation of p38 MAP kinase. Preincubation of cells with SB203580, a specific inhibitor of p38 inhibited DNA fragmentation induced by cell-permeable ceramide. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1555-1563
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• 2007

To idenifty effect of Bojungbangam-tang kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells. Cytotoxicity of cisplatin was detected in HK-2 cells and the value of IC50 is about $25\;{\mu}M$. The treatment of cisplatin to HK-2 showed the G2/M phase cell cycle arrest. The ethanol extract of Bojungbangam-tang kakambang (EBTKB), a new herbal prescription composed of ten crude herbs, inhibited cisplatin-induced G2/M phase arrest in HK-2 cells. EBTKB increased G0/G1 peak in cisplatin-treated HK-2 cells. p53, p21 and p27 expression were increased in cisplatin-treated HK-2 cells. Inhibitory effect of EBTKB on cisplatin-induced G2/M phase arrest was accomplished through inhibition of p53, p21 and p27 expression. Also, reduced CDK2 and cyclin A expression by cisplatin were increased by EBTKB, but cyclin E was not changed. Reduction of ERK activation and increment of p38 activation by cisplatin were increased ERK activation and decreased p38 activation by EBTKB. Cisplatin had no effect on JNK activation, but EBTKB increased JNK activation. These results can suggest that EBTKB inhibits cisplatin-induced G2/M phase arrest in HK-2 cell through reduction of p53-dependent p21 and p27 protein, ERK activation and p38 inactivation.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.100-100
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• 2002

• KSBB Journal
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• v.18 no.4
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• pp.329-334
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• 2003

The present study was aimed at investigating the regulatory mechanism in tissue-specific expression of insulin-like growth factor-I (IGF-I) gene. The expression of IGF-I gene was determined by a solution hybridization/RNase protection assay using total RNA prepared from rat liver or brain of various ages. The levels of IGF-I transcripts were increased in liver gradually after birth, but decreased in brain. By using an oligonucleotide (FRE) corresponding to the C/EBP binding site of the rat IGF-I exon 1, multiple forms of C/EBP${\alpha}$ and C/EBP${\beta}$ proteins, which have DNA-binding activity, were detected in the rat liver or brain. Western immunoblot and southwestern analyses show that p42$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\alpha}$/, p35$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\beta}$/, and p35$\^$C/EBP${\beta}$ form specific complexes with the IGF-I exon 1 oligonucleotide in liver nuclear extract and that p42$\^$C/EBP${\alpha}$/ and p38$\^$C/EBP${\beta}$/ form complexes in brain. These data suggest that the formation of FRE-C/EBP isoform complexes may play important roles in the tissue-specific regulation of IGF-I gene expression.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.757-767
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• 1999

Background: Diagnosis by smear and/or cultures of the Mycobacterium tuberculosis from body fluid or biopsy specimen is "Gold standard". However the sensitivity of the direct microscopy is relatively low and culture of mycobacteria is time consuming. Despite an explosion in the techniques of rapid identification of mycobacteria by molecular genetic means, it is laborious and expensive and then rapid, inexpensive serodiagnosis is interested in diagnosis of tuberculosis. But sensitivity and specificity of known serologic antigen is not full sufficient level and then new antigen develop and combination cocktails of new developed antigens by ELISA are needed. Method: To compare the efficacy of different mycobacterial specific antigen and to assess the applicability of the combination of several different antigens in the diagnosis of tuberculosis, five ELISA tests derived 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were evaluated in 57 active pulmonary patient and 24 inactive post-therapy follow up patient and 48 normal control. Results: The optical densities of ELISA test with 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were significantly higher in active tuberculosis cases than in normal control(P<0.001, P<0.001, P<0.027, P<0.001, P<0.001) and those with 16KDa, 38KDa were significant higher in active tuberculosis cases than in inactive post-therapy follow up cases(P<0.01. P<0.001) and those of 14KDa, 16KDa, 23KDa, 38KDa were significant higher in inactive post-therapy follow up cases than in normal control(P<0.008. P<0.01. P<0.006. P<0.001). The sensitivity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 42.1%, 43.9%, 15.8%, 28.0%, 70.2%, respectively and the specificity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 95.8%, 95.8%, 91.7%, 89.6%, 93.8%, respectively. The sensitivity and specificity of combination 38KDa with 16KDa was 87% and 93.7%. Conclusion: The sensitivity and specificity of new antigens for serodiagnosis of the tuberculosis still remains limited at around 70%, which makes its a poor diagnostic tool for disease confirmation. A combination of cocktail antigens provided by cut-off value adjustment for serodiagnosis of tuberculosis some improved diagnostic yield than single antigen serologic test.

• Molecules and Cells
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• v.23 no.1
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• pp.30-38
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• 2007

Dipyrithione (2, 2'-dithiobispyridine-1, 1'-dioxide, PTS2), a pyrithione derivate, is highly bactericidal and fungicidal. In this study we examined its apoptotic effect on HeLa cells. PTS2 induced HeLa cell death in a dose and time dependent manner. ERK1/2 and p38 were markedly activated, but little JNK1/2 activation was detected. Suppression of p38 activation by SB203580 reduced the extent of apoptosis of the HeLa cells and also prevented induction of p21, release of cytochrome c, and cleavage of caspase-3 and PARP. Inhibition of ERK1/2 with PD98059 increased apoptosis, indicating that ERK1/2 activation has an anti-apoptotic effect on PTS2-induced HeLa cell apoptosis. PTS2 also inhibited murine sarcoma 180 and hepatoma 22 tumor growth in an animal tumor model. Our findings indicate that PTS2 possesses anti-tumor activity, that caspase-3 and poly (ADP-ribose) polymerase (PARP) are involved in PTS2-induced HeLa cell apoptosis and that ERK1/2 and p38 have opposing effects on this apoptosis.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.77-90
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• 2003

The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide(LPS), sodium nitroprusside(SNP), hydrogen peroxide($H_2O_2$)-induced expressions of cyclooxygenase-2(COX-2), p38, jun N-terminal Kinase(JNK) and extra-signal response kinase(ERK) in RAW 264.7 cells, a murine macrophage cell line. Method : The expressions of COX-2, p38, JNK and ERK were determined by western blotting with corresponding antibodies. Results : 1. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly $H_2O_2$-induced expression of COX-2 compared with control, respectively. 2. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS, SNP and $H_2O_2$-induced expression of p38 compared with control, respectively. 3. The 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of JNK compared with control, respectively. All of bee venom inhibited insignificantly LPS and $H_2O_2$-induced expression of JNK compared with control, respectively. 4. The $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of ERK, the $0.5\;{\mu}g/ml$ of bee venom increased significantly $H_2O_2$-induced expression of ERK compared with control. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly LPS-induced expression of ERK compared with control, respectively.