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Taxol-Induced Apoptosis and Nuclear Translocation of Mitogen-Activated Protein (MAP) Kinase in HeLa Cells

  • Kim, Sung-Su;Kim, Yoon-Suk;Jung, Yon-Woo;Choi, Hyun-Il;Shim, Moon-Jeong;Kim, Tae-Ue
    • BMB Reports
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    • v.32 no.4
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    • pp.379-384
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    • 1999
  • Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects on the cell such as an increase in tyrosine phosphorylation of proteins and activation of mitogen-activated protein (MAP) kinase. This phosphorylated kinase translocates into the nucleus and phosphorylates its substrate c-jun, c-fos, ATF2, and ATF3. The MAP kinase family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. First examination was cytotoxicity and apoptosis-induced concentration with paclitaxel in HeLa cell. A half-maximal inhibition of cell proliferation ($IC_{50}$) occurred at 13 nM paclitaxel. When DNA fragmentation was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 24 h after a taxol (50 nM) addition to the cells. In addition, an apoptotic body was detected by electron microscopy. Taxol-treated cells were arrested at the S phase at 10 nM. Treatment of 50 nM taxol activated the extracellular signal-regulated protein kinase (ERK1), and a fraction of the activated MAP kinases entered the nucleus. It was also discovered that nucleus substrates c-jun was phosphorylated and activated in the cell. The activated ERK1 could subsequently translocate into the nucleus and phosphorylate its substrate c-jun as well. This study suggests that taxol-induced apoptosis might be related with signal transduction via MAP kinases.

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Sensor System for Multi-Point Monitoring Using Bending Loss of Single Mode Optical Fiber (단일 모드 광섬유의 굽힘손실을 이용한 다점 측정 센서 시스템)

  • Kim, Heon-Young;Kim, Dae-Hyun
    • Journal of the Korean Society for Nondestructive Testing
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    • v.35 no.1
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    • pp.39-45
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    • 2015
  • Applications of smart sensors have been extended to safety systems in the aerospace, transportation and civil engineering fields. In particular, structural health monitoring techniques using smart sensors have gradually become necessary and have been developed to prevent dangers to human life and damage to assets. Generally, smart sensors are based on electro-magnets and have several weaknesses, including electro-magnetic interference and distortion. Therefore, fiber optic sensors are an outstanding alternative to overcome the weaknesses of electro-magnetic sensors. However, they require expensive devices and complex systems. This paper proposes a new, affordable and simple sensor system that uses a single fiber to monitor pressures at multiple-points. Moreover, a prototype of the sensor system was manufactured and tested for a feasibility study. Based on the results of this experimental test, a relationship was carefully observed between the bend loss conditions and light-intensity. As a result, it was shown that impacts at multiple-points could be monitored.

Suppressive Effect of CheongGiGeoYangTang on Allergic Inflammation of RBL-2H3 Mast Cells and OVA/alum-sensitized Mice (청기거양탕(淸肌祛痒湯)의 RBL-2H3 비만세포와 OVA/alum 감작 생쥐의 알레르기 염증 반응 억제 효과)

  • Lee, Hye-Lim;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.26 no.1
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    • pp.1-15
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    • 2012
  • $CheongGiGeoYangTang$ has been used for anti-allergenic purpose. However there was no experimental study about its effect. Therefore, this study was designed to investigate the anti-allergenic effect of $CheongGiGeoYangTang$. Methods Modifiability of RBL-2H3 mast cells' IL-4, IL-13 was analyzed by qRT-PCR and ELISA. Also, the suppressive effect of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}B$ p65 transcription factors was observed by western blotting. OVA-specific IgE, IL-4 and IL-13 production in ovalbumin allergy model was examined as well. Results It was showed that the RBL-2H3 mast cells treated with $CheongGiGeoYangTang$ extract(CGGYT) was significantly suppressed mRNA expression, production of IL-4 and IL-13, and prominently inhibited the expression of transcription factors including GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 but not c-Jun. The administration of CGGYT was suppressed the amount of OVA-specific IgE, IL-4 and IL-13 in OVA/alum-sensitized mice. Conclusions We considered CGGYT would regulate the allergic inflammation as inhibition of IL-4 and IL-13 production in activated mast cells and Th2 cells.

Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

  • Jin, Su Hyun;Kim, Hyunsoo;Gu, Dong Ryun;Park, Keun Ha;Lee, Young Rae;Choi, Yongwon;Lee, Seoung Hoon
    • BMB Reports
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    • v.51 no.7
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    • pp.356-361
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    • 2018
  • Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of $NF-{\kappa}B$ ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

Inhibitory Effects of Boesenbergia pandurata on Age-Related Periodontal Inflammation and Alveolar Bone Loss in Fischer 344 Rats

  • Kim, Haebom;Kim, Changhee;Kim, Do Un;Chung, Hee Chul;Hwang, Jae-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.3
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    • pp.357-366
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    • 2018
  • Periodontitis, an infective disease caused by oral pathogens and the intrinsic aging process, results in the destruction of periodontal tissues and the loss of alveolar bone. This study investigated whether Boesenbergia pandurata extract (BPE) standardized with panduratin A exerted anti-periodontitis effects, using an aging model representative of naturally occurring periodontitis. In aged rats, the oral administration of BPE ($200mg{\cdot}kg^{-1}{\cdot}day^{-1}$) for 8 weeks significantly reduced the mRNA and protein expression of $interleukin-1{\beta}$, nuclear factor-kappa B, matrix metalloproteinase (MMP)-2, and MMP-8 in gingival tissues (p < 0.01). In alveolar bone, histological analysis with staining and micro-computed tomography revealed the attenuation of alveolar bone resorption in the BPE-treated aged group, which led to a significant reduction in the mRNA and protein expression of nuclear factor of activated T-cells c1 (NFATc1), c-Fos, tartrate-resistant acid phosphatase, and cathepsin K (p < 0.01). BPE not only increased the expression of osteoblast differentiation markers, such as alkaline phosphate, and collagen type I (COL1A1), but also increased the ratio of osteoprotegerin to RANKL. Collectively, the results strongly suggested that BPE is a natural resource for the prevention or treatment of periodontal diseases.

Inhibitory Effects of Panduratin A on Periodontitis-Induced Inflammation and Osteoclastogenesis through Inhibition of MAPK Pathways In Vitro

  • Kim, Haebom;Kim, Mi-Bo;Kim, Changhee;Hwang, Jae-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.2
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    • pp.190-198
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    • 2018
  • Periodontitis is an inflammatory disease caused by microbial lipopolysaccharide (LPS), destroying gingival tissues and alveolar bone in the periodontium. In the present study, we evaluated the anti-inflammatory and anti-osteoclastic effects of panduratin A, a chalcone compound isolated from Boesenbergia pandurata, in human gingival fibroblast-1 (HGF-1) and RAW 264.7 cells. Treatment of panduratin A to LPS-stimulated HGF-1 significantly reduced the expression of interleukin-$1{\beta}$ and nuclear factor-kappa B (NF-${\kappa}B$), subsequently leading to the inhibition of matrix metalloproteinase-2 (MMP-2) and MMP-8 compared with that in the LPS control ($^{**}p$ < 0.01). These anti-inflammatory responses were mediated by suppressing the mitogen-activated protein kinase (MAPK) signaling and activator protein-1 complex formation pathways. Moreover, receptor activator of NF-${\kappa}B$ ligand (RANKL)-stimulated RAW 264.7 cells treated with panduratin A showed significant inhibition of osteoclastic transcription factors such as nuclear factor of activated T-cells c1 and c-Fos as well as osteoclastic enzymes such as tartrate-resistant acid phosphatase and cathepsin K compared with those in the RANKL control ($^{**}p$ < 0.01). Similar to HGF-1, panduratin A suppressed osteoclastogenesis by controlling MAPK signaling pathways. Taken together, these results suggest that panduratin A could be a potential candidate for development as a natural anti-periodontitis agent.

JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38

  • Yi, Young-Su;Kim, Mi-Yeon;Cho, Jae Youl
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.345-352
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    • 2017
  • Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-$1{\beta}$ without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the $NF-{\kappa}B$ transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the $NF-{\kappa}B$ pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the $NF-{\kappa}B$ and AP-1 pathways, respectively.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

  • Choi, Dong-Ok;Yon, Chon-Il;Choi, Myoung-Ae;Park, Byung-Rim;Kim, Min-Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.4
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    • pp.181-185
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    • 2004
  • Extracellular regulated protein kinase1/2 (pERK1/2) is one of the major regulatory factors for transcription of the c-fos oncogene in neurons. The purpose of this study was to evaluate the expression of phosphorylated ERK1/2 within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following the acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2 in these nuclei occurred within 5 min after hemorrhage. However, in bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. Western blot confirmed the effect of bilateral labyrinthectomy on pERK1/2 protein expression in the medial vestibular nucleus 5 min after hemorrhage. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of ERK 1/2 in the VN.

Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract

  • Li, Liang;Park, Young-Ran;Shrestha, Saroj Kumar;Cho, Hyoung-Kwon;Soh, Yunjo
    • Journal of Microbiology and Biotechnology
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    • v.30 no.10
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    • pp.1543-1551
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    • 2020
  • Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPS-treated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

The Effect of Using of the Hotel Information System on the Service Quality (호텔정보시스템활용이 서비스품질에 미치는 영향)

  • Cho, Sun-Bai
    • Korean Business Review
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    • v.19 no.1
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    • pp.175-191
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    • 2006
  • The purpose of this study is to findout the effect of using of the hotel information system(HIS) on the hotel service quality. To show how important the using level of the information system in the hotel, we surveyed some domestic and overseas deluxe hotels. For an empirical analysis, Authors have collected 574 questionaires from 4 countries during Feburary to August, 2003. Factor Analysis and Regression Analysis were applied in this research. The results are as follows: There are a close relation between using level of the hotel information systems and service quality. Authors insists that to maximize service quality efficiency in the hotel, a balanced using level of the information system should be made in the following fields: front-office operating system(FOS), back-office operating system(BOS), outlet operating system(OOS) and interface operating system(IOS).

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