• Journal of Microbiology and Biotechnology
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• 제26권6호
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• pp.1063-1066
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• 2016

Longan (Dimocarpus longan Lour.) has been used as a traditional oriental medicine and possesses a number of physiological activities. In this study, we used cell-based herbal extract screening to identify longan fruit extract (LFE) as an activator of osteoblast differentiation. LFE up-regulated alkaline phosphatase (ALP) activity, induced mineralization, and activated Runx2 gene expression in MC3T3-E1 cells. Furthermore, treatment of MC3T3-E1 cells with LFE promoted the phosphorylation of extracellular signal-regulated kinase1/2 (Erk1/2); however, abrogation of Erk1/2 activation with PD98059 resulted in down-regulation of the phospho-SMAD1/5/8 and Runx2 levels, which in turn reduced the ALP activity. Our findings suggest that LFE exerts its osteogenic activity through activation of the ERK signaling pathway and may have potential as an herbal therapeutic or a preventive agent for the treatment of osteoporosis.

• Molecules and Cells
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• 제46권3호
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• pp.142-152
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• 2023

Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

• 대한의생명과학회지
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• 제22권2호
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• pp.60-64
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• 2016

In the pathogenesis of inflammatory diseases such as allergies, S100A8 acts as an important molecule and T lymphocytes are essential cytokine-releasing cells. In this study, we investigated the effect of S100A8 on release of cytokines, specifically MCP-1, IL-6, and IL-8 in T cells, and its associated signaling mechanism. S100A8 increased secretion of MCP-1, IL-6, and IL-8 in a time- and dose-dependent manner. Elevated secretion of MCP-1, IL-6, and IL-8 due to S100A8 was inhibited by the TLR4 inhibitor TLR4i, the PI3K inhibitor LY294002, the $PKC{\delta}$ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF-${\kappa}B$ inhibitor BAY-11-7085. S100A8 induced phosphorylation of ERK, p38 MAPK, and JNK in a time-dependent manner, and activation was suppressed by TLR4i, LY294002, and rottlerin. S100A8 induced NF-${\kappa}B$ activation by $I{\kappa}-B{\alpha}$ degradation, and NF-${\kappa}B$ activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, $PKC{\delta}$, MAPKs, and NF-${\kappa}B$ will contribute to elucidation of the S100A8-invovled mechanism.

• Clinical and Experimental Reproductive Medicine
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• 제30권1호
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• pp.5-14
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• 2003

Objective: Present study was aimed to verify the effect of granulocyte macrophage-colony stimulating factor (GM-CSF) in the preimplantation development of mouse embryos and the involvement of the mitogen activated protein kiase (MAPK) in the GM-CSF signaling. Methods: Two-cell embryos were cultured for 96 h in the presence or absence of GM-CSF (0, 0.4, 2, 10 ng/ml) and PD98059, a MEK inhibitor (10 ${\mu}M$). Morphological development, cell number per blastocyst, and apoptotic nuclei, were eamined. MAPK activity of embryonic immunoprecipitate by MAPK (ERK1/2) antibody was measured by in vitro phosphorylation of myelin basic protein. Results: At post hCG 122 h the embryonic development among the experimental groups was significantly different (p=0.018). The rate of blastocyst development and cell number per embryo were the highest in 2 ng/ml GM-CSF treatment group. The percent of apoptotic cells of the GM-CSF-treated embryos was the lowest among the group. In blastocysts, GM-CSF treatment transiently increased MAPK activity. PD098059 attenuated the effect of GM-CSF on the morphological development, increase in cell number per blastocyst, down regulation of apoptosis, and upregulation of MAPK activity, suggesting that activation of MAPK cascade possibly mediated the embryotropic effect of GM-CSF. Conclusion: This result suggested that GM-CSF potentiated the development of preimplantation mouse embryos by activation of MAPK.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.850-856
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• 2004

Intraneuronal deposition containing $\alpha$-synuclein is implicated in the pathogenesis of synuclein-opathies including Parkinsons disease (PD). Although it has been demonstrated that cytoplas-mic inclusions of wild type $\alpha$-synuclein are observed in the brain of PD patients and that $\alpha$-synuclein mutations such as A30P and A53T accelerate aggregate formation, the exact mech-anism by which $\alpha$-synuclein forms insoluble aggregates is still controversial. In the present study, to understand the possible involvement of tissue transglutaminase (tTG) in aggregate formation of $\alpha$-synuclein, SH-SY5Y cell lines stably expressing wild type or mutant (A30P or A53T) $\alpha$-synuclein were created and aggregate formation of $\alpha$-synuclein was observed upon activation of tTG. The data demonstrated that $\alpha$-synuclein negligibly interacted with tTG and that activation of tTG did not result in the aggregate formation of $\alpha$-synuclein in SH-SY5Y cells overexpressing either wild type or mutant $\alpha$-synuclein. In addition, $\alpha$-synuclein was not modi-fied by activated tTG in situ. These data suggest that tTG is unlikely to be a contributing factor to the formation of aggregates of $\alpha$-synuclein in a stable cell model.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.83-83
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• 2003

In our previous study, glucose deprivation was reported to induce the potentiated death and ATP loss in immunostimulated astroglia. And this vulnerability to glucose deprivation was due to overproduction of nitric oxide (NO) and hydrogen peroxide (H$_2$O$_2$). In the present study, the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in the glucose deprivation-induced death of immunostimulated astroglia was examined. We showed that immunostimulation with LPS+IFN-ν activated the ERKl/2 signal pathway and produced a large amount of NO and H$_2$O$_2$. Generation of NO and H$_2$O$_2$ in immunostimulated astroglia was mediated via ERK1/2 signal pathways, since addition of the ERK kinase (MEKl) inhibitor PD98059 reduced NO and H$_2$O$_2$production. ERK1/2 activation-mediated NO and H$_2$O$_2$ production is due to an activation of iNOS and NADPH oxidase, respectively. Finally, we found that glucose deprivation caused ATP depletion and the augmented death in immunostimulated astroglia, which was also prevented by PD98059 treatment. These results demonstrate that the ERK1/2 signal pathways play an important role in glucose deprivation induced the death in immunostimulated astroglia by regulating the generation of NO and H$_2$O$_2$.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2008년도 하계학술대회 논문집 Vol.9
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• pp.237-238
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• 2008

본 연구에서는 APD 소자 제작시 주로 쓰이는 RTA에 의한 Zn 확산방법에 사용할 경우 undoped InP의 V/III비율에 따른 Zn원자의 확산, 도핑, 오믹저항의 성장을 조사하였다. RTA에 의한 확산 및 활성화 열처리 시 도핑 농도의 프로파일은 확산열처리만 한 경우보다 활성화 처리한 경우 더 커짐을 볼 수 있었다. SIMS 결과 활성화 처리 후 표면쪽에 Zn원자의 약간의 결핍현상을 보이는 데 이는 표면쪽에 Zn원자의 탈착이 약간 이루어지는 것으로 보인다. 이 원인은 결과적으로 오믹저항의 증가를 가져왔다.

• The Korean Journal of Physiology and Pharmacology
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• 제6권3호
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• pp.165-169
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• 2002

We have previously demonstrated that phytoestrogens isolated from safflower seeds significantly attenuated bone loss in ovariectomized rats, and directly stimulated proliferation and differentiation of cultured osteoblastic cells. In an attempt to elucidate underlying cellular mechanisms, in the present study we investigated effects of $17{\beta}-estradiol\;(E_2)$ and phytoestrogens such as matairesinol and acacetin, a type of lignan and flavonoid, respectively, on activation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and ERK2, in cultured osteoblastic ROS 17/2.8 cells. Western blot analysis with anti-MAP kinase antibody showed that a wide range concentrations $(10^{-14}\;to\;10^{-6}\;M)\;of\;E_2$ as well as both phytoestrogens induced rapid and transient activation of ERK1/2 through phosphorylation within minutes. Maximum activation of MAP kinases by $E_2$ and phytoestrogens were observed at 10 and 15 min, respectively. $E_2-induced$ phosphorylation of ERK1/2 returned to the control level at 30 min, whereas phytoestrogen-induced phosphorylation was maintained at high level until 30 min. PD-98059, a highly selective inhibitor of MAP kinase, prevented phosphorylation of ERK1/2 in the cells treated either with $E_2$ or phytoestrogens. To examine a possible involvement of estrogen receptor in the activation process of MAP kinase, Western blot analysis was performed in the presence and absence of the estrogen receptor antagonists, ICI 182,780 and tamoxifen. These antagonists blocked MAP kinase phosphorylation induced not only by $E_2,$ but also by the phytoestrogens. To the best our knowledge, this study is the first to demonstrate that phytoestrogens such as flavonoid and lignan extracted from safflower seeds produce a rapid activation of MAP kinase, at least partially via membrane estrogen receptor of the cultured osteoblastic cells.

• Journal of Radiation Protection and Research
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• 제41권3호
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• pp.286-290
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• 2016

Background: Activation of air and water in the electron linear accelerator for medical use has not been considered severely. By the new Japanese regulation for protection of radiation hazard, it became indispensable to evaluate of activation of air and water in the accelerator room. The measurement of induced activity in air and water components in the electron energy region of 10 to 20 MeV is very difficult, because this energy region is close to the threshold energy region of photonuclear reactions. Then, we measured the photonuclear reaction yields of $^{13}N$, $^{15}O$, and $^{11}C$ by using the electron linear accelerator. Obtained data were compared with the data calculated by the Monte Carlo method. Materials and Methods: An activation experiment was performed at the Research Center for Electron Photon Science, Tohoku University. Highly purified $SiO_2$, $Si_3N_4$, and carbon disks were irradiated for 10 minutes by bremsstrahlung converted by a tungsten plate. Induced activity from C, N, and O was obtained. Monte Carlo calculation was performed using MCNP5 and AERY (DCHAIN-SP) to simulate the experimental condition. Cross section data were adopted the KAERI dataset. Results and Discussion: In our experiment in hospital, calculated values were not agreed with experimental values. It might be three possible reasons as the cause of this deference, such as irradiation energy, calculation procedure and cross section data. Obtained data of this work, calculated and experimental values were good agreement with each other within one order. In this work, we used KAERI dataset of photonuclear reaction instead of JENDL. Therefore, it was found that the photonuclear cross section data of light elements are most important for yield calculation in these reactions. Conclusion: Further improvement for calculation using a new dataset JENDL/PD-2015 and considering electron energy spreading will be needed.

• The Korean Journal of Physiology and Pharmacology
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• 제14권6호
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• pp.365-369
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• 2010

In this study, we examined whether melatonin promotes apoptotic cell death via p53 in prostate LNCaP cells. Melatonin treatment significantly curtailed the growth of LNCaP cells in a dose- and time-dependent manner. Melatonin treatment (0 to 3 mM) induced the fragmentation of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, caspase-8, and caspase-9. Moreover, melatonin markedly activated Bax expression and decreased Bcl-2 expression in dose increments. To investigate p53 and p21 expression, LNCaP cells were treated with 0 to 3 mM melatonin. Melatonin increased the expressions of p53, p21, and p27. Treatment with mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that the melatonin-induced apoptosis was p21-dependent, but ERK-independent. With the co-treatment of PD98059 and melatonin, the expression of p-p53, p21, and MDM2 did not decrease. These effects were opposite to the expression of p-p53, p21, and MDM2 observed with SP600125 and SB202190 treatments. Together, these results suggest that p53-dependent induction of JNK/p38 MAPK directly participates in apoptosis induced by melatonin.