• 제목/요약/키워드: Reduced mechanism

검색결과 2,190건 처리시간 0.028초

P2X and P2Y Receptors Mediate Contraction Induced by Electrical Field Stimulation in Feline Esophageal Smooth Muscle

  • Cho, Young-Rae;Jang, Hyeon-Soon;Kim, Won;Park, Sun-Young;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제14권5호
    • /
    • pp.311-316
    • /
    • 2010
  • It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 ($10^{-7}{\sim}10^{-4}M$), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue ($10^{-6}{\sim}10^{-4}M$), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist ${\alpha}$,${\beta}$-methylene 5'-adenosine triphosphate (${\alpha}{\beta}MeATP$, $10^{-7}{\sim}10^{-5}M$) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[${\beta}$-thio]diphosphate trilithium salt ($ADP{\beta}S$, $10^{-7}{\sim}10^{-5}M$) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,$N$-diethyl-D-${\beta}$,${\gamma}$- dibromomethylene 5'-triphosphate triammonium (ARL 67156, $10^{-4}M$) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.

이진탕 분획엑스가 synaptosomal NaK ATPase와 Ca ATPase의 활성도에 미치는 영향 (Effects of Ijingtang fractions on activities of NaK ATPase and Ca ATPase in rat brain synaptosome)

  • 조영욱;한승호;김창주;민병일;이태희;윤상협;오수명
    • 대한한의학회지
    • /
    • 제18권1호
    • /
    • pp.198-207
    • /
    • 1997
  • To explore the action mechanism of Ijintang in the brain, the authors investigated the effects of Ijintang fractions on MgNaK ATPase and MgCa ATPase in rat brain synaptosomes prepared from cerebral cortex. The activities of MgNaK ATPase and MgCa ATPase were assayed by the level of inorganic phosphate liberated from the hydrolysis of ATP. Fraction WH-95-7 at the concentration of $10^{-2}%$ decreased the activity of MgNaK ATPase about 34.1% and also reduced the activity of MgCa ATPase about 49.3% But, other fractions (WB-95-7, WC-95-7, MB-95-7, MC-95-7, MH-95-7) did not significantly changed the activities of the MgNaK ATPase and MgCa ATPase The decreased activity of MgNaK ATPase by WH-95-7 will decrease the rate of $Ca^{2+}$ efflux, probably via an Na-Ca exchange mechanism and will increase the rate of $Ca^{2+}$ entry by the depolarization of nerve terminals. The reduced activity of MgCa ATPase by WH-95-7 will result in the decreased efflux of $Ca^{2+}$. As a conclusion, it can be speculated that lithium elevates the intrasynaptosomal $Ca^{2+}$ concentration via inhibition of the activities of MgNaK ATPase and MgCa ATPase. and this increased $[Ca^{2+}]i$ will cause the release of neurotransmitters.

  • PDF

Licochalcone A가 대식세포주의 사이토카인 생성에 미치는 영향 (Effect of Licochalcone A on the Production of Cytokines in LPS-Activated RAW264.7 Macrophage Cells)

  • 이기세;이성호;조영창;윤구;천승훈;강복윤
    • 약학회지
    • /
    • 제53권6호
    • /
    • pp.321-327
    • /
    • 2009
  • Licochalcone A is a chalcone isolated from the roots of Glycyrrhiza inflate. In this study, we examined the effects of licochalonce A on the production of cytokines in LPS-activated macrophages. Licochalcone A inhibited the secretion of proinflammatory cytokines such as IL-1$\beta$, IL-6, and TNF-$\alpha$. The reduced secretion of proinflammatory cytokines is related to the differences in the mRNA expression of IL-1$\beta$, IL-6, and TNF-$\alpha$. Moreover, licochalcone A inhibited the mRNA expression of IL-12p40, IL-18, and IL-23p19. To investigate its mechanism, we performed gel shift assay. Licochalcone A reduced nuclear NF-${\kappa}B$ binding activity in LPS-activated RAW264.7 cells. Taken together, these results suggest that licochalcone A has anti-inflammatory effects in LPS-activated macrophages and its mechanism could be through the down-regulation of binding to the ${\kappa}B$ site.

청증보폐탕(淸蒸補肺湯)의 면역조절능(免疫調節能)을 통한 항천식(抗喘息) 효능(效能) (Immunological Modulation Mechanism of Chungzeungbopyetang(CBPT) in Asthma Induced Animal Model)

  • 박종광;최학주;김선빈;김동희
    • 혜화의학회지
    • /
    • 제17권2호
    • /
    • pp.69-86
    • /
    • 2008
  • In order to validate the objective efficacy of CBPT on anti-asthma and to develop effective therapeutics for asthma treatments, immunological modulatory mechanism was studied using animal model using OVA-Alum. The results are listed below. When treated with CBPT, survival rate of hFCs at 250 ug/ml was above 90%. AST and ALT, indicators of liver function measurements were in the normal range. Compared to the control group, CBPT treated group showed significant reduction in liver weights at both 400 and 200 mg/kg, and significant decrease of total liver cells at 400 mg/kg. Significant increase in CD4+ and CD8+ cells in DLN was observed in the CBPT treated group. Slight increase in CD3+, CD4+/CD25+ cells were also observed. On the other hand, CBPT significantly reduced the CD3+/CD69+ cell numbers at both concentrations. Slight decrease of CD19+ cells was also observed. CBPT significantly reduced the CD3e+/CD69+, CCR3+ and CD11b+/Gr-1+ cells in lung tissues at both doses. However, significant decrease of CD3e+ and B220+/IgE+ cells was only observed at 400 mg/kg dosed group. The results above strongly suggest the anti-asthmatic effect of CBPT through immunological modulation. By using various concentrations of CBPT, broader clinical applications of CBPT on anti-asthmatic treatment can be developed. The EBM database should provide valuable information in the development of drugs for asthma treatments.

  • PDF

몰약(沒藥)이 자궁경부암세포(子宮經部癌細胞)(HeLa Cell)의 Apoptosis에 미치는 영향(影響) (Myrrha-induced Apoptosis in Human Cervical Carcinoma HeLa Cells)

  • 박종규;조옥현;김송백;조한백
    • 대한한방부인과학회지
    • /
    • 제19권1호
    • /
    • pp.97-110
    • /
    • 2006
  • Purpose : To address the ability of Myrrha (MY) to induce cell death, we investigated the effect of MY on apoptosis. In human cervical carcinoma HeLa cells, apoptosis occurred following MY exposure in a dose-dependent manner. Methods : We have tested several kinds of anti-oxidants to investigate the MY-induced apoptotic mechanism. Among the anti-oxidants, N-acetyl cysteine(NAC) or reduced glutathione (GSH) protects MY-induced apoptosis. NAC is an aminothiol and synthetic precursor of intracellular cysteine and GSH. To confirm the role of GSH in MY-induced apoptosis, methionine and cystathionine-glutathione extrusion inhibitors were treated in the presence of MY. Results : NAC, GSH, methionine or cystathionine led to protective effect against MY-induced apoptosis in HeLa cells. The GSH and GSH-associated reagents regulate MY-induced cytochrome c release and the resultant caspase-3 activation. Furthermore, the two specific inhibitors of carrier-mediated GSH extrusion, methionine and cystathionine demonstrate GSH extrusion occurs via a specific mechanism. While decreasing GSH extrusion and protecting against MY-induced apoptosis, methionine and cystathionine failed to exert anti-apoptotic activity in cells previously deprived of GSH. Conclusion : the target of the protection is indeed GSH extrusion. This shows that the protective effect is achieved by forcing GSH to stay within the cells during apoptogenic treatment. All this evidence indicates the extrusion of GSH precedes andis responsible for the apoptosis, probably by altering the intracellular redox state, thus giving a rationale for the development of redox-dependent apoptosis in MY-treated human cervical carcinoma HeLa cells.

  • PDF

$Co_2$ Corrosion Mechanism of Carbon Steel in the Presence of Acetate and Acetic Acid

  • Liu, D.;Fu, C.Y.;Chen, Z.Y.;Guo, X.P.
    • Corrosion Science and Technology
    • /
    • 제6권5호
    • /
    • pp.227-232
    • /
    • 2007
  • The corrosion behavior of carbon steel (N80) in carbon dioxide saturated 1%NaCl solution with and without acetic acid or acetate was investigated by weight-loss test, electrochemical methods (polarization curve, Electrochemical impedance spectroscopy). The major objective is to make clear that the effect of acetic acid and acetate on the corrosion of carbon steel in $Co_2$ environments. The results indicate that either acetic acid or acetate accelerates cathodic reducing reaction, facilitates dissolution of corrosion products on carbon steel, and so promotes the corrosion rate of carbon steel in carbon dioxide saturated NaCl solution. All Nyquist Plots are consisting of a capacitive loop in high frequency region, an inductive loop in medial frequency region and a capacitive arc in low frequency region. The high frequency capacitive loop, medial frequency inductive loop and low frequency capacitive arc are corresponding to the electron transfer reaction, the formation/adsorption of intermediates and dissolution of corrosion products respectively. All arc of the measured impedance reduced with the increase of the concentration of Ac-, especially HAc. However, the same phenomenon is not notable after reducing pH value by adding HCl. HAc is a stronger proton donor and can be reduced directly by electrochemical reaction firstly. Ac- can't participate in electrochemistry reaction directly, but $Ac^-$ an hydrate easily to create HAc in carbon dioxide saturated environments. HAc is as catalyst in $Co_2$ corrosion. As a result, the corrosion rate was accelerated in the presence of acetate ion even pH value of solution increased.

Dehydroepiandrosterone supplement increases malate dehydrogenase activity and decreases NADPH-dependent antioxidant enzyme activity in rat hepatocellular carcinogenesis

  • Kim, Jee-Won;Kim, Sook-Hee;Choi, Hay-Mie
    • Nutrition Research and Practice
    • /
    • 제2권2호
    • /
    • pp.80-84
    • /
    • 2008
  • Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

실내가스폭발 해석에 관한 연구 (A study on the analysis of domestic gas explosion)

  • 김상섭;채재우
    • 한국가스학회지
    • /
    • 제7권4호
    • /
    • pp.24-29
    • /
    • 2003
  • 실내에서 가스 폭발시 피해를 예측하기 위해서 폭발 화염면의 전파를 수치해석을 통해 해석했다. 확산방정식에 의해 가스누출에 의한 실내의 가스확산분포를 구했으며, 문헌에서 선택한 누출의 초기조건을 사용했다. 화염온도를 계산하기 위해 각 가스 혼합비에 따른 엔탈피와 화학식에 대한 reduced mechanism을 사용했으며 문헌에서 찾은 각 가스의 농도 별 층류 연소속도를 혼합가스의 층류연소속도에 적용시켰다. k-$\epsilon$ 모델에서 난류 에너지를 층류연소속도와 결합시켜 난류화염 전파속도를 모델링 했다. 화염면의 전파를 분석하기 위해 실내의 위치에는 직각, 화염면의 전파에는 원통좌표계를 사용했다. 유리창의 파손에 의한 화염전파면의 변화에 따른 압력상승 요인을 해석하였으며, 창문의 크기에 따라서 점화위치에 따른 실내 압력상승의 영향이 서로 다르게 나타나는 결과를 얻었다.

  • PDF

Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling

  • Ham, Won-Kook;Lee, Eun-Jung;Jeon, Myung Shin;Kim, Hae-Young;Agrahari, Gaurav;An, Eun-Joo;Bang, Chul Hwan;Kim, Doo-Sik;Kim, Tae-Yoon
    • BMB Reports
    • /
    • 제54권2호
    • /
    • pp.142-147
    • /
    • 2021
  • Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

Failure characteristics and mechanical mechanism of study on red sandstone with combined defects

  • Chen, Bing;Xia, Zhiguo;Xu, Yadong;Liu, Shuai;Liu, Xingzong
    • Geomechanics and Engineering
    • /
    • 제24권2호
    • /
    • pp.179-191
    • /
    • 2021
  • In this study, the strength and failure mechanism of red sandstones with combined defects were investigated by uniaxial compression tests on red sandstones with different crack angles using two-dimensional particle flow code numerical software, and their mechanical parameters and failure process were studied and analyzed. The results showed that the mechanical characteristics such as peak strength, peak strain, and elastic modulus of the samples with prefabricated combined defects were significantly inferior than those of the intact samples. With increasing crack angle from 15° to 60°, the weakening area of cracks increased, elastic modulus, peak strength, and peak strain gradually reduced, the total number of cracks increased, and more strain energy was released. In addition, the samples underwent initial brittle failure to plastic failure stage, and the failure form was more significant, leading to peeling phenomenon. However, with increasing crack angle from 75° to 90°, the crack-hole combination shared the stress concentration at the tip of the crack-crack combination, resulted in a gradual increase in elastic modulus, peak strain and peak strength, but a decrease in the number of total cracks, the release of strain energy reduced, the plastic failure state weakened, and the spalling phenomenon slowed down. On this basis, the samples with 30° and 45° crack-crack combination were selected for further experimental investigation. Through comparative analysis between the experimental and simulation results, the failure strength and final failure mode with cracks propagation of samples were found to be relatively similar.