• The Journal of Korean Physical Therapy
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• v.20 no.3
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• pp.53-59
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• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

• Korean Journal of Animal Reproduction
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• v.19 no.2
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• pp.95-104
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• 1995

Mouse mammary epithelial cells(NMuMG) were maintained onto 6-well plates (3$\times$105 cells/well) or chambered slide (1$\times$104 cells/well), in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 hours, DMNB (1$\mu$M) was added and exposed to UV light (300nm, 3 second pulse) after 2 hours from DMNB addition in order to activate DMNB which induces a rapid transient increase in intracellular cAMP upon UV irradiation. EGF (100ng/ml) and/or IGF-I (10ng/ml) were treated at the time of UV irradiation. Nuclear labeling index was estimated as percent of nuclear labeled cells(percent of S phase of cells) by incorporation of 3H-thymidine into DNA(1 hour pulse with 1$\mu$Ci/ml). DMNB(1$\mu$M), EGF (100ng/ml) and/or IGF-I (10ng/ml) signifciantly increased nuclear labeling index than those of control (P<0.05). Addition of DMNB＋EGF or DMNB＋EGF＋IGF-I showed the interaction effect in nuclear labeling index (P<0.05). Protein kinase A activities by addition of EGF, IGF-I or EGF＋IGF-I were 10.5, 9.8 or 9.4 unit/mg protein, respectively, and no statistical difference was found in comparison with control (P>0.05). Additon of DMNB＋EGF showed the moderate interaction effect on tyrosyl kinase activity (P<0.1). In the fluorography analysis, there were no specific protein phosphorylation patterns were found at 1 or 15 minute by addition of DMNB. EGF and/or IGF-I. These results suggest that the interaction effect in nuclear labeling index by addition DMNB and EGF could be mediated through the modulation of tyrosyl kinase activity by cAMP.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.2
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• pp.139-145
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• 2020

Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

• Journal of Integrative Natural Science
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• v.10 no.2
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• pp.95-104
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• 2017

Proviral Integration site of Moloney (Pim) murine Leukemia virus kinases is a serine/threonine specific protein kinase. It is largely involved in cell survival and proliferation. Pim-1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Over expression of Pim-1 kinase is observed in a range of malignancies and various solid cancers. High level of Pim-1 expression is seen in myeloma, acute myeloid leukemia, prostate cancer and liver carcinomas. Hence, Pim-1 is considered as an interesting cancer target. In the present study, we have performed region-focused CoMFA study on a series of imidazopyridazine derivatives as Pim-1 kinase inhibitors. A statistically acceptable region-focused CoMFA model ($q^2=0.571$; ONC=3; $r^2=0.909$) was developed. The model was then validated using Bootsrapping and progressive sampling. The contour map highlighted the regions favorable to increase the activity. Bulky substitutions in $R^2$ position of the phenyl ring could increase the activity. Similarly, small negative substitution in the $R^1$ position of the Pyridine ring could increase the activity considerably. Our results will be useful to design novel Pim-1 kinase inhibitors of this series.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2004.10a
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• pp.48-52
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• 2004

We have found the role of rice mitogen-activated protein kinase kinase kinase (MAPKKK), OsEDR1, as controling hypersensitive response (HR) and increased disease resistance to rice blast fungus Magnaporthe grisea. Generation of transgenic rice plants through introduction of the over-expression construct of OsEDR1 using Agrobacterium-mediated transformation results in lesion mimic phenotype. Up-regulation of defense mechanism was detected through detection of increased transcription level of rice PBZ1 and PR1a. Inoculation of rice blast fungus on the lesion mimic transgenic lines displayed significantly increased resistance. The disease symptoms were arrested like HR responses which are commonly detected in the incompatible interactions. High accumulation of phenolic compounds around developing lesions was detected under UV light. There was variation among transgenic lines on the timing of lesion progression as well as the lesion numbers on the rice leaves. Transgenic lines with few lesions also show increased resistance as well as equal amount of grain yields compared to that of wild type rice cultivar Nipponbare. This is the first report of the MAPKKK as a positive regulator molecule on defense mechanism through inducing HR-like cell death lesion mimic phenotype. The application of OsEDR1 is highly expected for the development of resistant cultivars against rice pathogens.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.189-198
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• 2015

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.365-368
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• 2008

Calcium entry through $Ca_v3.2Ca^{2+}$ channels plays essential roles for various physiological events including thalamic oscillation, muscle contraction, hormone secretion, and sperm acrosomal reaction. In this study, we examined how protein tyrosine phosphatases or protein tyrosine kinases affect $Ca_v3.2Ca^{2+}$ channels reconstituted in Xenopus oocytes. We found that $Ca_v3.2$ channel activity was reduced by 25% in response to phenylarsine oxide (tyrosine phosphatase inhibitor), whereas it was augmented by 19% in response to Tyr A47 or herbimycin A (tyrosine kinase inhibitors). However, other biophysical properties of $Ca_v3.2$ currents were not significantly changed by the drugs. These results imply that $Ca_v3.2$ channel activity is capable of being increased by activation of tyrosine phosphatases, but is decreased by activation of tyrosine kinases.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.589-599
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• 2019

Background: Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. Methods: 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and realtime polymerase chain reaction, respectively. Results: Rg1 dramatically enhanced expression of brown adipocyte-especific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5' adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Conclusions: Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.51-59
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• 2021

Periodontal disease is an inflammatory disease that affects the destruction of the bone supporting the tooth and connective tissues surrounding it. Periodontal ligament fibroblasts (PDLFs) induce overexpression of matrix metalloproteinase (MMP) involved in periodontal disease's inflammatory destruction. Osteoclasts take part in physiological bone remodeling, but they are also involved in bone destruction in many kinds of bone diseases, including osteoporosis and periodontal disease. This study examined the effect of baicalin on proteolytic enzymes' production and secretion of inflammatory cytokines in PDLFs and RAW 264.7 cells under the lipopolysaccharide (LPS)-induced inflammatory conditions. Baicalin inhibited the expression of the protein, MMP-1 and MMP-2, without affecting PDLFs' cell viability, suggesting its possibility because of the inhibition of phosphorylation activation of mitogen-activated protein kinase's p38, and the signal transduction process of nuclear factor κB (NFκB)-related protein. Also, baicalin reduced the expression of MMP-8 and MMP-9 in RAW 264.7 cells. This reduction is thought to be due to the inhibition of the signal transduction process of NFκB-related proteins affected by inhibiting p65RelA phosphorylation. Also, baicalin inhibited the secretion of nitric oxide and interleukin-6 induced by LPS in RAW 264.7 cells. These results suggest that baicalin inhibits connective tissue destruction in periodontal disease. The inhibition of periodontal tissue destruction may be a therapeutic strategy for treating inflammatory periodontal-diseased patients.