• 대한본초학회지
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• 제22권2호
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• pp.147-153
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• 2007

Objectives : Sophora flavescens (SF) is widely used in traditional herbal medicine in Korea and is well recognized for its anti-inflammatory effect. However, its effect on Tumornecrosis factor alpha (Tnf) production in BV2 microglial cell is not yet known. Methods : We investigated the effect of SF on the production and expression of Tnf, a well known inflammatory mediator, in lipopolysaccaride (LPS)-activated BV2 microglial cells. Results : The LPS-induced Tnf production was markedly reduced by treatment with SF (50 ${\mu}g/ml$). In reverse transcription polymerase chain reaction (RT-PCR) analysis, SF suppressed the LPS activated expression of Tnf mRNA. In addition, Western blot analysis confirmed that SF suppressed the expression of Tnf. Sophora flavescens also inhibited the LPS-induced phosphylation of extracellular signal-regulated kinases (ERK), which mediate the Tnfproduction signaling pathway whereas LPS-induced phosphylation of p38 mitogen activated protein kinase (p38 MAPK), and c-Jun NH2-terminal kinases (JNK) was not inhibited by SF, which implies that SF suppresses LPS-induced Tnf production via the ERK mediated pathway. Conclusion : Taken together, these findings indicated that SF inhibits LPS-induce Tnf production, and that this inhibitory effect is mediated via the ERK pathway.

• Journal of Microbiology and Biotechnology
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• 제26권7호
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• pp.1311-1319
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• 2016

Alternaria brassicicola (Schwein.) invades Brassicaceae and causes black spot disease, significantly lowering productivity. Mitogen-activated protein kinases (MAPKs) and their upstream kinases, including MAPK kinases (MAPKKs) and MAPKK kinases (MAPKKK), comprise one of the most important signaling pathways determining the pathogenicity of diverse plant pathogens. The AbSte7 gene in the genome of A. brassicicola was predicted to be a homolog of yeast Ste7, a MAPKK; therefore, the function was characterized by generating null mutant strains with a gene replacement method. AbSte7 replacement mutants (RMs) had a slower growth rate and altered colony morphology compared with the wild-type strain. Disruption of the AbSte7 gene resulted in defects in conidiation and melanin accumulation. AbSte7 was also involved in the resistance pathways in salt and oxidative stress, working to negatively regulate salt tolerance and positively regulate oxidative stress. Pathogenicity assays revealed that AbSte7 RMs could not infect intact cabbage leaves, but only formed very small lesions in wounded leaves, whereas typical lesions appeared on both intact and wounded leaves inoculated with the wild-type strain. As the first studied MAPKK in A. brassicicola, these data strongly suggest that the AbSte7 gene is an essential element for the growth, development, and pathogenicity of A. brassicicola.

• Molecules and Cells
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• 제22권1호
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• pp.104-112
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• 2006

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-${\kappa}B$ by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-${\kappa}B$ increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-${\kappa}B$ pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.451-456
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• 2001

In rat hippocampus, kainic acid (KA; 10 mg/kg; i.p.) increased the phosphorylated forms of ERK1/2 (p-ERK1/2) and Jun kinase1 (p-JNK1), but not p-JNK2 and p38 (p-p38). The preadministration with cycloheximide (CHX; 5 mg/kg; i.p.) inhibited KA-induced increase of p-JNK1, but not p-ERK1/2. Surprisingly, the phosphorylated upstream MAP kinase kinases (p-MKKs) were not correlated with their downstream MAP kinases. The basal p-MKK1/2 levels were completely abolished by KA, which were reversed by CHX. In addition, p-MKK4 and p-MKK3/6 levels were enhanced by CHX alone, but were attenuated by KA. Thus, our results showed that KA increased the p-ERK and p-JNK levels in rat hippocampus, which were not parallel with their classical upstreamal kinases.

• Animal Bioscience
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• 제35권9호
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• pp.1444-1453
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• 2022

Objective: Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. Methods: The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 [ERK1/2] activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. Results: It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. Conclusion: Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.547-553
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• 1997

It has been known that activation of tyrosine kinases is involved in signal transduction. Role of the tyrosine kinase in vascular smooth muscle contraction was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy, one week after which they were subcutaneously implanted with DOCA (200 mg/kg) and supplied with 1% NaCl and 0.2% KCl drinking water for $4{\sim}6$ weeks. Control rats were treated the same except for that no DOCA was implanted. Helical strips of carotid arteries were mounted in organ baths for measurement of isometric force development. Genistein was used as a tyrosine kinase inhibitor. Concentration-response curves to 5-hydroxytryptamine (5-HT) shifted to the right by genistein in both DOCA-salt hypertensive and control rats. Although the sensitivity to genistein was similar between the two groups, the maximum force generation by 5-HT was less inhibited by genistein in arteries from DOCA-salt hypertensive rats than in those from controls. Genistein-induced relaxations were attenuated in arteries from DOCA-salt rats. Genistein affected the contraction to phorbol 12, 13-dibutyrate (PDBu) neither in DOCA-salt nor in control arteries. These observations suggest that tyrosine kinase is involved in 5-HT-induced vascular contraction, of which role is reduced in DOCA-salt hypertension.

• Animal cells and systems
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• 제6권1호
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• pp.1-12
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• 2002

A role of Src family protein Tyrosine kinases (SFK) as mediators of receptor-ligand initiated responses is well established. Well documented, but less well understood is the role of SFK in cellular reaction to stresses. Evidence from the wide variety of experimental systems indicates that SFK mediate responses to all major classes of stress, including oxidation, DNA damage, mechanical impacts, and protein denaturing. SFK may be activated by stresses directly or via regulatory circuits whose identity is not yet fully understood. Depending on the cell type and the nature of activating stimulus, SFK may activate known downstream signaling cascades leading to cell survival, proliferation, cytoskeletal rearrangement, and apoptosis; the identity of these cascades is discussed. As in the case of receptor-initiated signaling, roles of individual SFK in various stress response may be redundant or non-redundant. Although signals generated by different stresses are generally transduced via distinct SFK pathways, these pathways may overlap or exhibit crosstalk. In some cell types stress-induced activation of SFK promotes survival and inhibits apoptosis, whereas the opposite may be true for other cell types. Stress responses constitute a new and rapidly developing area of SFK-mediated signaling.

• Parasites, Hosts and Diseases
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• 제48권4호
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• pp.285-290
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• 2010

Tyrosine kinases are one of the most important regulators for intracellular signal transduction related to inflammatory responses. However, there are no reports describing the effects of tyrosine kinases on neutrophil apoptosis induced by Entamoeba histolytica, In this study, isolated human neutrophils from peripheral blood were incubated with live trophozoites in the presence or absence of tyrosine kinase inhibitors. Entamoeba-induced receptor shedding of CD16 and PS externalization in neutrophils were inhibited by pre-incubation of neutrophils with the broad-spectrum tyrosine kinase inhibitor genistein or the Src family kinase inhibitor PP2. Entamoeba-induced ROS production was also inhibited by genistein or PP2, Moreover, genistein and PP2 blocked the phosphorylation of ERK and p38 MAPK in neutrophils induced by E. histolytica. These results suggest that Src tyrosine kinases may participate in the signaling event for ROS-dependent activation of MAPKs during neutrophil apoptosis induced by E. histolytica.

• BMB Reports
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• 제34권5호
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• pp.421-427
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• 2001

Osteoclasts, cells primarily involved in bone resorption, originate from the hematopoietic precursor cells of the monocyte/macrophage lineage and differentiate into multinucleated mature forms. We developed an in vitro osteoclast culture system using embryonic chicken bone marrow cells. This culture system can be utilized in studies on the differentiation and function of osteoclasts. Phosphatidylinositol 3-kinase (PI3-kinase) and mitogen-activated protein kinases (MAPKs) have been implicated in diverse cellular functions including proliferation, migration, and survival. Using the developed avian osteoclast culture system, we examined the involvement of these kinases in osteoclast differentiation by employing specific inhibitors of the kinases. We Found that the inhibition of the PI 3-kinase, p38, or ERK interfered with osteoclast formation, suggesting that the signaling pathways that involve these molecules participate in the process of chicken osteoclast differentiation.

• 한국발생생물학회지:발생과생식
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• 제18권1호
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• pp.65-71
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• 2014

Cell cycle process is regulated by a number of protein kinases and among them, serine/threonine kinases carry phosphate group from ATP to substrates. The most important three kinase families are Cyclin-dependent kinase (Cdk), Polo-like kinase (Plk), and Aurora kinase. Polo-like kinase family consists of 5 members (Plk1-Plk5) and they are involved in multiple functions in eukaryotic cell division. It regulates a variety of aspects such as, centrosome maturation, checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many other features. Recently, it has been reported that Plks are related to tumor development and over-expressed in many kinds of tumor cells. When injected the anti-Plk antibody into human cells, the cells show aneuploidy, and if inhibit Plks, most of the mitotic cell division does not proceed properly. For that reasons, many inhibitors of Plk have been recently emerged as new target for remedy of the cancer therapeutic research. In this paper, we reviewed briefly the characteristics of Plk families and how Plks work in regulating cell cycles and cancer formation, and the possibilities of Plks as target for cancer therapy.