• 한국동물위생학회지
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• 제31권4호
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• pp.457-463
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• 2008

The sex steroid hormone estradiol-$17{\beta}(E_2)$ mediate their biological effects on development, differentiation and maintenance of reproductive tract and other target tissue through gene regulation by nuclear steroid receptors. Although the importance of $E_2$ in many physiological process has been reported, but little is known about the effects of $E_2$ on primary cultured chicken hepatocyte. therefore, in the present study, we have examined the effect of $E_2$ on cell proliferation and it's related signal cascades. $E_2$ increase $[^3H]$-thymidine incorporation in time-(${\leq}8hr$) and dose-($10^{-10}M$)dependent manner and treatment of $E_2$ increased the phosphorylation of p44/43 MAPKs(p44/42 mitogen-activated protein kinase) and JNK(c-Jun N-terminal kinase) in a time dependent manner. In addition, PD98059(p44/42 blocker, $10^{-5}M$), SP600125(JNK blocker, $10^{-6}M$) blocked the estrogen-induced increase in $[^3H]$-thymidine incorporation. In conclusion, $E_2$ stimulates the proliferation of primary cultured chicken hepatocytes and this action is mediated by p44/42 MAPKs and JNK signal transduction pathway.

• 동의생리병리학회지
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• 제24권3호
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• pp.410-415
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• 2010

The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Belamcanda chinensis (BC) on the RAW 264.7 cells. To evaluate the anti-inflammatory effects of BC, we examined the cytokine productions including nitric oxide (NO), interleukin (IL)-1b, IL-6 and tumor necrosis factor-a (TNF-a) in lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kB) using Western blot. BC inhibited LPS-induced production of NO, IL-6 and TNF-a but not of IL-1b in RAW 264.7 cells. BC respectively inhibited the activation of MAPKs such as c-Jun NH2-terminal kinase (JNK) and p38 but not of extracelluar signal-regulated kinase (ERK 1/2) and NF-kB in the LPS-stimulated RAW 264.7 cells. Taken together, Our results showed that BC down-regulated LPS-induced NO, IL-6 and TNF-a productions mainly through JNK and p38 MAPK pathway.

• BMB Reports
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• 제44권6호
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• pp.399-404
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• 2011

In this study, powder of Orostachys japonicus A. Berger (O. japonicus) was extracted with 95% ethyl alcohol and fractionated using a series of organic solvents, including n-hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n-butanol (BuOH), and water ($H_2O$). We investigated the anti-inflammatory effects of these O. japonicus extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Their effects on the expression of inflammatory mediators and transcription factors were analyzed by Western blotting. DCM fraction significantly inhibited formation of reactive oxygen species (ROS) as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Phosphorylation of the pro-inflammatory transcription factor complex nuclear factor-kappa B (NF-${\kappa}$B) p65 and expression of inducible nitric oxide synthase (iNOS), one of its downstream proteins, were also suppressed by DCM fraction. These effects were regulated by upsteam proteins in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways. Taken together, our data suggest that O. japonicus could be used as a potential source for anti-inflammatory agents.

• 대한한방부인과학회지
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• 제36권1호
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• pp.23-34
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• 2023

Objectives: This study was conducted to confirm the anticancer effect of Torilis Japonica (TJ) on cervical cancer and to determine whether the effect was apoptosis. Methods: In this study, the effect of TJ extract on toxicity, mitochondrial morphology, nuclear morphological changes, Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathway were investigated in HeLa cell, human cervical cancer cell. Results: The cytotoxicity, ratio of cells with nuclear changes to the total number of cells, and P38 phosphorylation increased in a concentration-dependent manner after administration of TJ extract. The length of mitochondria and ERK phosphorylation in HeLa cells decreased in a concentration-dependent manner after administration of TJ extract. Conclusions: TJ extract has an anticancer effect on cervical cancer cells, which is presumed to be due to apoptosis, and showed potential as a future cervical cancer treatment.

• Journal of Acupuncture Research
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• 제32권3호
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• pp.83-93
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• 2015

Objectives : The purpose of this study was to evaluate whether acupuncture at $SP_6$ attenuates esophageal inflammation on refluxed-induced esophagitis. Methods : Acupuncture at $SP_6$ was stimulated by acupuncture torsion technique for 30 seconds four times every hour after an operation induced reflux esophagitis(RE), and its effects were assessed in comparison with RE rats without acupuncture, and normal rats. Results : $SP_6$ acupuncture stimulation markedly ameliorated mucosal damage in the histological evaluation. Reflux-induced esophagitis rats exhibited the down-regulation of antioxidant-related protein expression levels such as heme oxygenase-1(HO-1) in the esophagitis; however, the associated levels with $SP_6$ acupuncture stimulation were significantly higher than those in RE rats without acupuncture stimulation. Moreover, $SP_6$ acupuncture stimulation significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase(MAPK)-related signaling pathways. The increased protein expressions of inflammatory mediators, cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS), by nuclear factor-kappa B(NF-kB) activation were significantly suppressed through $SP_6$ acupuncture stimulation. Conclusions : Our findings support the therapeutic evidence for $SP_6$ acupuncture stimulation alleviating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway.

• Animal Bioscience
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• 제36권2호
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• pp.295-306
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• 2023

Objective: Inhibiting the p38 mitogen-activated protein kinase (MAPK) signaling pathway delays differentiation and increases proliferation of muscle stem cells in most species. Here, we aimed to investigate the effect of p38 inhibitor (p38i) treatment on the proliferation and differentiation of chicken muscle stem cells. Methods: Chicken muscle stem cells were collected from the muscle tissues of Hy-line Brown chicken embryos at embryonic day 18, then isolated by the preplating method. Cells were cultured for 4 days in growth medium supplemented with dimethyl sulfoxide or 1, 10, 20 μM of p38i, then subcultured for up to 4 passages. Differentiation was induced for 3 days with differentiation medium. Each treatment was replicated 3 times. Results: The proliferation and mRNA expression of paired box 7 gene and myogenic factor 5 gene, as well as the mRNA expression of myogenic differentiation marker gene myogenin were significantly higher in p38i-treated cultures than in control (p<0.05), but immunofluorescence staining and mRNA expression of myosin heavy chain (MHC) were not significantly different between the two groups. Oil red O staining of accumulated lipid droplets in differentiated cell cultures revealed a higher lipid density in p38i-treated cultures than in control; however, the expression of the adipogenic marker gene peroxisome proliferator activated receptor gamma was not significantly different between the two groups. Conclusion: p38 inhibition in chicken muscle stem cells improves cell proliferation, but the effects on myogenic differentiation and lipid accumulation require additional analysis. Further studies are needed on the chicken p38-MAPK pathway to understand the muscle and fat development mechanism.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3239-3245
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• 2012

Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.517-524
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• 2015

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.137-142
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• 2008

Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. $C_2$-ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the $C_2$-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited $C_2$-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the $C_2$-ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit $C_2$-ceramide induced contraction via PKC and MAPK dependent pathway.

• Archives of Pharmacal Research
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• 제23권6호
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• pp.605-612
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• 2000

Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase IIgene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 $\mu\textrm{m}$with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 $\mu\textrm{m}$ to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP.