• 대한한방부인과학회지
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• 제20권3호
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• pp.91-110
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• 2007

Purpose : These experiments were undertaken to evaluate the effect of administration of Palmultang on ovarian functions and differential gene expressions related cell viabilities caspase-3, MAPK and MPG in female mice. Materials and Methods : We administered the Palmultang to 6-week-old female ICR mice for 4, 8, or 12 days. The female mice were injected PMSG and hCG for ovarian hyperstimulation. And then recovered ovaries were minced and extracted mRNA and analyzed cell viability related gene expression. We chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. To compare the differences, we set a control group treated with plain water at the same volume by the same way. Results : In case of administration of Palmultang, the mean number of total ovulated oocytes and the number of morphologically normal oocytes increased significantly compared to a control group. We were also examined the embryonic developmental competence in vitro. The administration of Palmultang in a concentration with 10 and 100 mg/ml were beneficial effect of embryonic development in preimplantation period. The administration of Palmultang play a role of prevention of cell apoptosis and DNA damages and also increased cell proliferation resulted in ovarian functions. Conclusion : From our results suggested that the medication of Palmultang has beneficial effect on reproductive functions of female mice via prevention of cell apoptosis and DNA damaging and promotion of cell proliferation.

• BMB Reports
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• 제46권4호
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• pp.213-218
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• 2013

Members of the colony stimulating factor cytokine family play important roles in macrophage activation and recruitment to inflammatory lesions. Among them, granulocyte-macrophage colony stimulating factor (GM-CSF) is known to be associated with immune response to mycobacterial infection. However, the mechanism through which Mycobacterium tuberculosis (MTB) affects the expression of GM-CSF is poorly understood. Using PMA-differentiated THP-1 cells, we found that MTB infection increased GM-CSF mRNA expression in a dose-dependent manner. Induction of GM-CSF mRNA expression peaked 6 h after infection, declining gradually thereafter and returning to its basal levels at 72 h. Secretion of GM-CSF protein was also elevated by MTB infection. The increase in mRNA expression and protein secretion of GM-CSF caused by MTB was inhibited in cells treated with inhibitors of p38 MAPK, mitogen-activated protein kinase kinase (MEK-1), and PI3-K. These results suggest that up-regulation of GM-CSF by MTB is mediated via the PI3-K/MEK1/p38 MAPK-associated signaling pathway.

• Journal of Nutrition and Health
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• 제41권3호
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• pp.224-231
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• 2008

본 연구는 십자화과 채소의 섭취로 체내유용 물질인 인돌이 전립선암 세포 PC3 cell의 항전이 효과 기전에 미치는 영향에 대하여 알아보았다. 인돌은 전립선암 세포중식을 농도 의존적으로 억제하였으며 인돌에 의한 세포 사멸의 영향과 관계없이 MMP-2, -9의 활성과 전사수준 및 단백질 발현을 억제하였다. 역으로 MMP활성 억제 물질인 TIMP-1,-2의 발현이 인돌 첨가에 의해 증가하였다. $NF{-\kappa}B$의 upstream에 존재하는 MAPK signaling 유전자인 ERK1/2, p38, JNK 발현이 인돌처리로 인산화를 억제하였다. 그리고 전립선암 세포 PC3 침윤성이 인돌 처리 시 유의적으로 감소하였다. 결론적으로 인돌은 PC3 인체 전립선암 세포의 전이 과정을 MAPK phthway를 통한 MMP 활성과 발현 억제, TIMP 발현 증가로 암 세포 전이 억제를 하는 것 으로 나타나 암 전이 억제 식품으로 가능성을 제시한다.

• Parasites, Hosts and Diseases
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• 제55권6호
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• pp.613-622
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• 2017

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

• Molecules and Cells
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• 제25권3호
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.

• 대한한방부인과학회지
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• 제20권2호
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• pp.1-24
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• 2007

Purpose : These experiments were undertaken to evaluate the effect of adminis tration of JokyungSan on ovarian functions and differential gene expressions related cell viabilities caspase-3, MAPK and MPG in female mice. Methods : We administered the JokyungSan to 6-week-old female ICR mice for 4, 8, or 12 days. The female mice were injected PMSG and hCG for ovarian hyperstimulation. We chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. To compare the differences, we set a control group treated with plain water at the same volume by the same way. Results : In case of 4-day administration of JokyungSan, the mean number of total ovulated oocytes and the number of morphologically normal oocytes increased significantly compared to a control group. The administration of JokyungSan, were beneficial effect of embryonic development in preimplantation period and play a role of prevention of cell apoptosis and DNA damages and also increased cell proliferation resulted in ovarian functions. Conclusion : From our results suggested that the medication of JokyungSan has beneficial effect on reproductive functions of female mice via prevention of cell apoptosis and DNA damaging and promotion of cell proliferation.

• Molecules and Cells
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• 제26권1호
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• pp.41-47
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• 2008

Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracelluar stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved $T{\times}Y$ motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase. However, the mechanism by which both residues are phosphorylated continues to remain elusive. In the budding yeast, Saccharomyces cerevisiae, Fus3 MAPK is involved in the mating signaling pathway. In order to elucidate the functional mechanism of MAPK activation, we quantitatively profiled phosphorylation of the $T{\times}Y$ motif in Fus3 using mass spectrometry (MS). We used synthetic heavy stable isotope-labeled phosphopeptides and nonphosphopeptides corresponding to the proteolytic $T{\times}Y$ motif of Fus3 and accompanying data-dependent tandem MS to quantitatively monitor dynamic changes in the phosphorylation events of MAPK. Phosphospecific immunoblotting and the MS data suggested that the tyrosine residue is dynamically phosphorylated upon stimulation and that this leads to dual phosphorylation. In contrast, the magnitude of threonine phosphorylation did not change significantly. However, the absence of a threonine residue leads to hyperphosphorylation of the tyrosine residue in the unstimulated condition, suggesting that the threonine residue contributes to the control of signaling noise.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.88-88
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• 2020

Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng. In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG. WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1β, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition. Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.259-266
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• 2020

Cardiovascular diseases are the primary reason of mortality, among which myocardial infarction (MI) is the most dominant and prevalent. This study was considered to examine D-Limonene protective action against isoproterenol (ISO) induced MI. Wister male rats were dispersed into four groups. Normal and D-Limonene control group in which rats administered saline or D-Limonene. ISO control animals were administered saline for 21 days then challenged with ISO (85 mg/kg, subcutaneously) on 20th and 21st day for MI induction. D-Limonene pretreated group in which animals were pretreated with D-Limonene 50 mg/kg orally for 21 days then administered ISO on 20th and 21st day. MI prompted variations were assessed by myocardial infarction area determination, blood pressure (BP) alterations, cardiac injury biomarkers and inflammatory mediators measurements. For more depth investigation, both the apoptotic status was evaluated via measuring mRNA expression of Bcl-2 and Bax as well as mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signal transduction were investigated via Western blotting. MI group revealed significant infarcted area, blood pressure alterations, myocardial injury enzymes intensification together with inflammatory cytokines amplification. MI was associated with activation of MAPK-ERK signal pathway and apoptotic status within the myocardium. On the other hand, pretreated with D-Limonene demonstrated deterred infracted area, reduced myocardial enzymes, improved BP indices, lessened inflammatory levels. Furthermore, D-Limonene pretreatment caused a decline in MAPK proteins pathway and Bax relative mRNA expression, while intensifying Bcl-2 mRNA expression promoting that D-Limonene may constrain MI induced myocardial apoptosis. D-Limonene mitigated MI injury through MAPK/NF-κB pathway inhibition and anti-apoptotic effect.

• Journal of Periodontal and Implant Science
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• 제34권3호
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• pp.489-498
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• 2004

Recent studies have demonstrated that human periodontal ligament cells express receptor activation of nuclear factor ${\kappa}B$ ligand (RANKL) which enhances the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The purpose of this study is to determine the effects of p38 MAPK and JNK kinase upon regulating RANKL and OPG in response to $IL-1{\beta}$(l ng/ml) in rat periodontal ligament cells. Soluble RANKL was measured by immunoassay. The effects of p38 MAPK on RANKL and OPG expression was determined by RT-PCR. The results were as follows: 1. Periodontal ligament cells which stimulated by $IL-1{\beta}$ increased soluble RANKL synthesis by dose-dependent pattern. 2. p38 MAP kinase inhibitor (SB203580) showed regulation of soluble RANKL expression by dose-dependent manners. 3. p38 MAP kinase inhibitor (SB203580) regulated the expression of RANKL, but it dose regulate the expresseion of OPG. 4. JNK (c-jun $NH_2-terminal$ kinase) inhibitor (PD98059) did not regulate mRANKL and mOPG. These results suggested that p38 MAPK play a significant role in RANKL gene expression.