• Title/Summary/Keyword: $A_2$ inhibitor

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Honokiol : A Noncompetitive Tyrosinase Inhibitor from Magnoliae Cortex

  • Tian, Yu-Hua;Kang, Tai-Hyun;Kim, Hyun-Chul;Kim, Youn-Chul
    • Natural Product Sciences
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    • v.11 no.2
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    • pp.89-91
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    • 2005
  • Effect of the neolignans, honokiol (1) and magnolol (2), isolated from Magnoliae Cortex on mushroom tyrosinase activity was investigated in vitro using L-tyrosine as a substrate. Honokiol (1) inhibited tyrosinase activity significantly in a concentration-dependent manner, on the other hand, magnolol (2) did not show tyrosinase inhibitory effect. Honokiol exhibited tyrosinase inhibitory effect with $IC_{50}$ value of $67.9\;{\mu}M$, and proved to act as a non-competitive inhibitor by the analysis of Lineweaver-Burk plot.

Role of Spinal Adenosine $A_2$ Receptor in the cardiovascular Regulation in Rats (흰쥐에서 실혈관 조절기전에 대한 척수의 Adenosine $A_2$수용체의 역할)

  • 문삼영;신현진;신인철;고현철;엄애선;박정로;김범수;강주섭
    • Biomolecules & Therapeutics
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    • v.8 no.4
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    • pp.325-331
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    • 2000
  • The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.

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Involvement of PI3K and MMP1 in PDGF-induced Migration of Human Adipose-derived Stem Cells

  • Lim, Yoonhwa;Lee, Minji;Jeong, Hyeju;Kim, Haekwon
    • Development and Reproduction
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    • v.21 no.2
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    • pp.167-180
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    • 2017
  • Human adult stem cells have widely been examined for their clinical application including their wound healing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

Cu CMP Property by Addition of Corrosion Inhibitor and Complexing Agent (부식 방지제와 Complexing Agent 첨가에 따른 Cu CMP 특성)

  • Kim, In-Pyo;Kim, Nam-Hoon;Kim, Sang-Yong;Lee, Cheol-In;Eom, Joon-Cheol;Chang, Eui-Goo
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2003.07a
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    • pp.343-346
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    • 2003
  • A systematic study of Cu CMP in terms of the effect of slurry chemicals(oxidizer, corrosion inhibitor, complexing agent) on the process characteristics has been performed. In acidic media, a corrosion inhibitor, benzotriazole(BTA) and tolytriazol(TTA) was used to control the removal rate and avoid isotropic etching. When complexing agent is added with $H_2O_2$ 2wt% in the slurry, a corrosion rate was presented very good. Most of in, it was appeared that BTA is possible to be replaced by TTA. The tartaric acid was distinguished for the effect among complexing agents. n we apply this results to copper CMP process, it is thought that we will be able to obtain better yield.

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Isolation of Proteinase Inhibitor II Genes from Potato (감자로부터 단백질분해효소 억제제 II 유전자의 분리)

  • 이종섭
    • Journal of Plant Biology
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    • v.32 no.2
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    • pp.79-87
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    • 1989
  • Southern hybridization of genomic DNAs with radioactively labeled cDNA of tomato proteinase inhibitor II revealed that proteinase inhibitor II proteins in potato plants are encoded by a family of about 10 related sequences. Screening of potato EcoRI genomic library with the cDNA resulted in isolation of 13 recombinant phage clones which carry 3 different genomic regions. Of these clones, clones 8, 18, and 39 were subjected to restriction mapping and subcloning. Further characterization of the subclones of clones 8, 18 and 39 indicated that two inhibitor II genes are present on a 8.0 kb EcoRI fragment of clone 8, one on 3.3 and 0.8 kb EcoRI fragments of clone 18 and two genes on a 13.5 kb EcoRI fragment of clone 39.

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Alpha-alkylcysteines as Inhibitors for Carboxypeptidase A. Synthesis, Evaluation, and Implication for Inhibitor Design Strategy

  • Lee, Hyun-Soo;Kim, Dong-H.
    • Bulletin of the Korean Chemical Society
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    • v.23 no.4
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    • pp.593-597
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    • 2002
  • (R,S)- and (R)-2-Benzylcysteine (1) and (R,S)-2-phenethylcysteine (2) were synthesized and evaluated as inhibitors for carboxypeptidase A (CPA) with the expectation that these compounds exhibit improved inhibitory activities over 2-benzyl-3-mercaptopropanoic acid (BMPA), a potent CPA competitive inhibitor, possibly having additional interactions of their amino group with the carboxylate of Glu-270 of the enzyme upon binding to CPA. Contrary to the expectation, however, the CPA inhibitory potencies of these compounds were found to be much reduced compared with that of BMPA, suggesting that the amino group in the inhibitors rather exerts steric hindrance in binding of these inhibitors to CPA.

A Case of Angioedema Induced by Angiotensin-Converting Enzyme Inhibitor (Angiotensin-Converting Enzyme Inhibitor(ACE Inhibitor)에 의해 유발된 안면부 맥관부종(angioedema) 치험례)

  • Hsia, Yu-Chun;Jung, Ki-Yong;Baik, Jong-Woo;Kim, Dong-Woo;Park, Jong-Hyung;Jun, Chan-Yong;Choi, You-Kyung
    • The Journal of Internal Korean Medicine
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    • v.28 no.2
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    • pp.399-407
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    • 2007
  • Angioedema is a localized transient swelling of sudden onset that can occur in the face, lips, tongue, hand, feet, respiratory system and gastrointestinal system. Angioedema is classified as allergy, hereditary, idiopathic or induced by medication as like aspirin, nonsteroidal anti-inflammatory agents, opiates, antibiotics, and angiotensin-converting enzyme. Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. This drug is commonly associated with angioedema which may be potentially life threatening. We experienced a case of angioedema induced by ACE inhibitor (angiotensin-converting enzyme inhibitor) in a 74-year-old patient who took ACE inhibitor to control hypertension during hospitalization. We thought the angioedema in the face had relation to myenzhong (面腫, mienjong) in oriental medicine. Weiling-tang (Wiryung-tang) was effective for angioedema in the face. As a result the symptoms disappeared rapidly. After 6 days, the patient's symptoms had notably improved.

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Lovastatin Induces Apoptotic Cell Death by Activation of Intracellular Ca2+ Signal in HepG2 Human Hepatoma Cells

  • Lee, Yong-Soo
    • Biomolecules & Therapeutics
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    • v.15 no.3
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    • pp.137-144
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    • 2007
  • Although lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase, has been shown to have anti-cancer actions, the effect on human hepatoma cells was not investigated. Moreover, the exact mechanism of this action is not fully understood. In this study we investigated the mechanism by which lovastatin induces apoptosis using HepG2 human hepatoblastoma cells. Lovastatin induced apoptotic cell death in a dose-dependent manner in the cells, assessed by the flow cytometric analysis. Treatment with mevalonic acid, a precursor of cholesterol, did not significantly suppress the lovastatin-induced apoptosis. Lovastatin induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and apoptosis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blocked these actions of lovastatin. In addition, the lovastatin-induced apoptosis was significantly reduced by a calpain inhibitor, a broad spectrum caspase inhibitor z-VAD-fmk and inhibitors specific for caspase-9 and caspase-3 (z-LEHD-fmk and z-DEVD-fmk, respectively), but not by an inhibitor specific for caspase-8 (z-IETD-fmk). Collectively, these results suggest that lovastatin induced apoptosis of HepG2 hepatoma cells through intracellular $Ca^{2+}$ release and calpain activation, leading to triggering mitochondrial apoptotic pathway. These results further suggest that lovastatin may be valuable for the therapeutic management of human hepatoma.

Effects of Trypsin Inhibitors on Oleic acid Induced Acute Pancreatitis in Dogs (개에서 Oleic acid로 유발시킨 급성췌장염에 대한 Trypsin inhibitor의 투여효과)

  • 윤영민;최희인;조명행
    • Biomolecules & Therapeutics
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    • v.5 no.2
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    • pp.158-164
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    • 1997
  • To investigate the effects of trypsin inhibitors, aprotinin and urinary trypsin inhibitor (UTI), on the cute pancreatitis, this study was carried out in dogs of acute pancreatitis induced by oleic acid (0.28 mg/kg). Administration with aprotinin and UTI seemed to have a therapeutic effect on the clinical sign, ultrasonographic finding, histopathologic finding. But in amylase and lipase activity, there were no significant differences among three groups.

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Synthesis and biological activity of 4,5-polymethylenepyrazole-derived HMG-CoA reductase inhibitors

  • Kim, Jin-Il;Choi, Young-Hee;Yurngdong Jahng
    • Archives of Pharmacal Research
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    • v.20 no.2
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    • pp.158-170
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    • 1997
  • New HMG-CoA reductase inhibitors, in which 3-substituted 4, 5-polymethylenepyrazoles are employed as a hydrophobic anchor connected to tetrahydro-4-hydroxy-2H-pyran-2-one by a two-carbon bridge, were designed and synthesized to exhibit significant inhibitory activity comparable to mevinolin. The most potent enzyme inhibitor $(11cc, IC_{50}=0.01{\mu}M)$ is 4-fold more potent than lovastatin.

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