• Title/Summary/Keyword: PAR2

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Par-4 Modulates Cell Migration through Inhibition of MMP-2 Activity in Human Renal Carcinoma Caki Cells (인간 신장암 Caki세포에서 Par-4에 의한 MMP-2 활성 저해를 통한 세포 이동 조절)

  • Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.26 no.5
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    • pp.614-619
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    • 2016
  • The prostate-apoptosis-response-gene-4 (Par-4) protein has been identified as an effector of cell death in response to various apoptotic stimuli in prostate cancer cells. We found that overexpression of Par-4 by stable transfection inhibits cell migration and invasion in Caki cells. The expression of various matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we investigated whether ectopic expression of Par-4 modulates MMP-2 expression and activity in human renal carcinoma Caki cells. We found that overexpression of Par-4 markedly inhibited MMP-2 activity, but not MMP-9 activity. However, loss of the leucine zipper domain of Par-4 (Par-4 ΔLZ#1 and #2) did not inhibit MMP-2 activity. Further, knock-down of Par-4 with the corresponding siRNA resulted in increased invasion and metastasis of renal carcinoma Caki cells. Interestingly, overexpression or knock-down of Par-4 did not affect the expression levels of MMP-2 mRNA. Taken together, our findings suggest that Par-4 may inhibit MMP-2 activity through its post-transcriptional regulation in renal carcinoma Caki cells.

Role of Protease Activated Receptor 2 (PAR2) in Aspergillus Protease Allergen Induces Th2 Related Airway Inflammatory Response (Aspergillus 단백분해효소 알러젠에 의해 유도된 Th2 관련 기도염증반응에서 protease activated receptor 2 (PAR2)의 역할)

  • Yu, Hak-Sun
    • Journal of Life Science
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    • v.20 no.4
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    • pp.503-510
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    • 2010
  • Most allergens have protease activities, suggesting that proteases may be a key link between Th2-type immune reactions in allergic responses. Protease activated receptor (PAR) 2 is activated via the proteolytic cleavage of its N-terminal domain by proteinases. To know the role of PAR2 in Aspergillus protease allergen activated Th2 immune responses in airway epithelial cells, we investigated and compared immune cell recruitment and level of chemokines and cytokines between PAR2 knock out (KO) mice and wild type (WT) mice. There were evident immune cell infiltrations into the bronchial alveolar lavage fluid (BALF) of WT mice, but the infiltrations in PAR2 KO mice were significantly lowered than those of WT mice. The IL-25, TSLP, and eotaxin gene expressions were profoundly increased after Aspergillus protease, but their expression was significantly lowered in PAR2 KO mice in this study. Compared to PAR2 KO mice, OVA specific IgE concentrations in serum of WT mice were quite increased; moreover, the IgE level of PAR2 KO mice was lower than in WT mice. The IL-25 expression by Aspergillus protease stimulation was significantly reduced by p38 specific inhibitor treatment. In this study, we determined that Th2 response was initiated with IL-25 and TSLP mRNA up-regulation in lung epithelial cells via PAR2 after Aspergillus protease allergen treatment.

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

  • Kim, Young-Hwan;Ahn, Duck-Sun;Kim, Myeong Ok;Joeng, Ji-Hyun;Chung, Seungsoo
    • Molecules and Cells
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    • v.37 no.11
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    • pp.804-811
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    • 2014
  • The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type $Ca^{2+}$ currents ($I_{Ca-N}$) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated $Ca^{2+}$ currents ($I_{Ca}$), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on $I_{Ca}$. This PAR-2-induced inhibition was almost completely prevented by ${\omega}$-CgTx, a potent N-type $Ca^{2+}$ channel blocker, suggesting the involvement of N-type $Ca^{2+}$ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited $I_{Ca-N}$ in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ${\omega}$-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type $Ca^{2+}$ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type $Ca^{2+}$ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.

Evaluation of hydrogen recombination characteristics of a PAR using SPARC PAR experimental results

  • Jongtae Kim;Jaehoon Jung
    • Nuclear Engineering and Technology
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    • v.55 no.12
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    • pp.4382-4394
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    • 2023
  • Passive auto-catalytic recombiners (PARs) are widely used to mitigate a hydrogen hazard. The first step to evaluate the hydrogen safety by PARs is to obtain qualified test data of the PARs for validation of their analytical model. SPARC PAR tests SP8 and SP9 were conducted to evaluate the hydrogen recombination characteristics of a honeycomb-shaped catalyst PAR. To obtain the hydrogen recombination rate from the PAR test data, two methods, Method-1 and Method-2, introduced by the THAI project, were applied. Since a large gradient of hydrogen concentration developed during hydrogen injection can cause a large error in the hydrogen mass obtained by integrating the measured hydrogen concentrations, a gate was installed at the PAR inlet to homogenize hydrogen in the test vessel before the PAR operation in the tests. A computational fluid dynamics (CFD) code with a PAR model was also applied to evaluate the characteristics of the PAR recombination according to the PAR inlet conditions, and the results were compared with those from Method-1 and Method-2. It was confirmed that the recombination rates from Method-1 require a correction factor to be compatible with results from Method-2 and the CFD simulation in the case of the SPARC-PAR tests.

Polarographic Behavior of Azo Series Organic Compounds (Ⅰ). Reduction of 4-(2-Pyridylazo)resorcinol in Acetonitrile (Azo계 유기화합물의 폴라로그래프법적 거동 (제1보). 아세토니트릴 중에서 4-(2-Pyridylazo) resorcinol의 환원)

  • Heung Lark Lee;Zun Ung Bae
    • Journal of the Korean Chemical Society
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    • v.26 no.6
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    • pp.389-395
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    • 1982
  • The polarographic behavior of 4-(2-pyridylazo)-resorcinol(PAR) in acetonitrile solution was studied. In order to investigate the type of reduction current at every reduction step, dependence of limiting current on the height of mercury head, solution temperature, and concentration of PAR have been examined. The results were shown that the reduction current was controlled by diffusion. And the effect of proton donor such as water and phenol on DC polarograms of PAR and the reversibility of every reduction wave have been evaluated. Based on the experimental results, the polarographic reduction of PAR in acetonitrile solution occurred in two one-electron steps.

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Effect of Supplemental Lighting in Different Lighting Intensity on Pyruvic Acid and Sugar Content in Onion(Allium cepa L.) (양파재배 시 보광정도에 따른 pyruvic acid와 당 함량)

  • Lee, Eun-Ju;Jeon, Jae-Kyung;Suh, Jun-Kyu
    • Journal of Bio-Environment Control
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    • v.17 no.4
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    • pp.266-272
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    • 2008
  • The aim of this study was to investigate the effect of supplemental lighting with different lighting intensity during growth on the sugar and pyruvic acid content of onion bulbs. As the result of comparison with growth, the content of pyruvic acid and sugar at harvest, supplemental lightening condition showed better growth, lower pyruvic acid content and higher sugar content than control. As to the growth at harvest according to lightening condition, 'Josaeng-ssundeobol' showed better growth as the lightening increased and 'Damrojunggab' had no difference above $12{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR. 'Josaeng-ssundeobol' contained much more content of pyruvic acid and sugar than 'Damrojunggab'. 'Josaeng-ssundeobol' had the lowest pyruvic acid content in $24{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR and 'Damrojunggab' had no difference above the $12{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR. The sugar content of 'Josaeng-ssundeobol' had no big difference above $18{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR and that of 'Damrojunggab' had no big difference above $12{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR. Desirable indicator to select individuals for the onion breeding is to select individuals that has low pyruvic acid content and high sweetness. Therefore, it will be possible to produce sweet onion conditioned on light supplement over $18{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR in 'Josaeng-ssundeobol' and over $12{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$ PAR in 'Damrojunggab'.

Inhibitory Effect of Mouse Paw Edema by Solanum melongena Aqueous Extract (노랑가지 물추출물에 의한 생쥐 발바닥 부종의 억제효과)

  • 김대기;백옥선;임종필;이영미
    • YAKHAK HOEJI
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    • v.47 no.5
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    • pp.325-330
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    • 2003
  • Solanum melongena L. (Solanaceae) has anti-oxidant, analgesic, and hypolipidemic effects. We previously showed that Solanum melongena (SM) aqueous extract inhibits mast cell-mediated allergic reactions. The activation of protease-activated receptor-2 (PAR-2) induces acute inflammation in rat hindpaw. In the present study, we investigated the effects of the SM aqueous extract on mouse paw edema induced by PAR2 agonists. Trypsin or trans-cinnamoyl-LIGRLO-NH$_2$ (tc-NH$_2$), PAR-2 agonists, was injected into the hind paw of mice to induce paw edema. SM aqueous extract (1, 5, 10, and 100 mg/kg) was orally administered 1 hr before induction of paw edema. SM aqueous extract (5, 10, and 100 mg/kg) significantly inhibited both paw edema and vascular permeability in the dose-dependent manner. Furthermore, SM aqueous extract (10 mg/kg) significantly inhibited PAR-2 agonist-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-$\alpha$ expression in paw tissue compared to that of saline. These results suggest that SM aqueous extract may be useful for treatment of PAR-2-mediated inflammation.

The Treatment Change of PAR(Peer Assessment Rating) Index and Cephalometric Measurements in Class I Malocclusion Patients (제 I 급 부정교합 환자에서 치료전후 PAR지수와 두부방사선계측치의 변화)

  • Kim, Hyeon-Hye;Lee, Ky-Heon;Kim, Jong-Chul
    • The korean journal of orthodontics
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    • v.29 no.2 s.73
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    • pp.277-284
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    • 1999
  • The purpose of this study was to evaluate the relation between the treatment duration and cephalometric measurements and the PAR index in Class I malocclusion patients. In 100 Class I malocclusion patients, PAR score and cephalometric measurements were taken from study model and cephalometric radiographs and analyzed statistically. The results of this study were obtained as follows: 1. treatment duration was correlated with extraction and pre PAR index. 2. ANB, FMA, FMIA and IMPA exhibited positive correlation between pre PAR index and pretreatment cephalometric measurements. 3. $\underline{1}$ to FP exhibited positive correlation between post PAR index and posttreatment cephalometric measurements, and $\overline{1}$ to FP exhibited negative correlation. 4. $\underline{1}$ to SN, IIA and $\overline{1}$ to FP exhibited positive correlation between ${\%}\;PAR$ reduction and the change of cephalometric measurements and FMA FMIA, WITS and UL exhibited negative correlation. The results of this study indicate that PAR index taken from study model relate with items concerned with upper and lower incisors, and there are the tendency that pretreatment PAR index are larger in the patients with large Am value and hyperdivergent face.

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Evaluation of orthodontic treatment outcomes and post-treatment changes by the PAR index (PAR 지수를 이용한 교정치료 결과의 평가에 관한 연구)

  • Cheong, Soo-Bong;Park, Young-Guk
    • The korean journal of orthodontics
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    • v.31 no.4 s.87
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    • pp.393-401
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    • 2001
  • The purposes of this study were to assess the treatment results in orthodontic department, Kyung Hee University, to evaluate the occlusion at 2 year follow-up control, in relation to the original malocclusion, and changes occurring in the follow-up period, and to determine whether treatment and posttreatment changes of the PAR index were related to the original Angle classification Dental study casts of 25 patients in permanent dentition were evaluated using Peer Assessment Rating (PAR) index. The PAR index was measured at the pretreatment stage, immediately after treatment, and at 2 yews posttreatment. The following results were obtained : 1. The treatment reduced the PAR index by 85.05% and it indicates that KHDC clinic has a high standard of treatment 2. The follow-up result of 75.40% PAR score reduction implies a gain of 9.55% of posttreatment PAR score during follow-up period. 3. There is no relationship between the treatment changes of the PAR index and the orignal Angle classification.

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Prostate Apoptosis Response-4 (Par-4) as a Cancer Therapeutic Target (암 치료 표적으로써 prostate apoptosis response-4 (Par-4))

  • Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.25 no.8
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    • pp.947-952
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    • 2015
  • Prostate apoptosis response-4 (Par-4) was originally identified in androgen-independent prostate cancer cells undergoing apoptosis. Par-4 is ubiquitously expressed in normal cells and tissues, but it is downregulated in several types of cancers. Par-4 is a 38 kDa tumor suppressor protein encoded by the PARW gene. Par-4 promotes apoptosis in a variety of cancerous cells, but not in normal cells. In this review, we focused on the structure, expression and function of Par-4 in apoptotic signaling pathway. Functional domains of Par-4 include two nuclear localization sequences (NLS), a leucine zipper (LZ) domain, a nuclear export sequence (NES) and selective for apoptosis in cancer cell (SAC) domain. Many studies have underlined the importance of Par-4 in preventing cancer development. The activity of Par-4 is differently regulated by localization of intracellular and extracellular Par-4. Intracellular Par-4 inhibits Akt- and NF-κB-mediated cell survival pathways and downregulates Bcl-2 expression. Extracellular Par-4 activates the extrinsic apoptotic pathway by binding to cell surface receptor GRP78, a stress response protein that is in the endoplasmic reticulum (ER). Endogenous Par-4 sensitizes cancer cells to various apoptotic stimuli, while exogenous Par-4 enhances SAC domain-dependent apoptosis in cancer cells, but not normal cells. Therefore, Par-4 is an attractive target for cancer therapy.