• Title/Summary/Keyword: Cyclic nucleotides

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Quality characteristics of enzymatic anchovy hydrolysates (멸치 효소 가수분해물의 품질특성)

  • Kang, C.S.;Jeong, D.S.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.14 no.1
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    • pp.93-105
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    • 2012
  • This study was carried out to prepare anchovy hydrolysates by using Alcalase, Neutrase and Protamex, and to investigate its quality characteristics. The major free amino acids were glutamic acid and lysine. The total amino acid content of anchovy hydrolysate were glutamic acid(12.6%), lysine(8.56%), valine(7.06%), aspartic acid(5.73%). Major nucleotides content of anchov hydrolysate were 5'-IMP (22.462 mg/100g), 5'-GMP (18.674 mg/100g) and 5'-UMP (1.25 mg/100g). Histamine content of anchovy hydrolysate was 18.1 mg/100g. These results suggested that anchovy hydrolysate could be used as a sauce of basic seasoning.

Screening Test(I) of Several Antipsychotic Agents on NO Formation (수종 정신병치료제들의 NO형성에 대한 검색(I))

  • Lee, Jong-Hwa;EI-fakahany, Esam E.
    • The Korean Journal of Pharmacology
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    • v.30 no.3
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    • pp.343-349
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    • 1994
  • A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

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Modulation of Large Conductance $Ca^{2+}-activated$ $K^+4$ Channel of Skin Fibroblast (CRL-1474) by Cyclic Nucleotides

  • Yun, Ji-Hyun;Kim, Seung-Tae;Bang, Hyo-Weon
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.2
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    • pp.131-135
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    • 2005
  • Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in $Ca^{2+}$ homeostasis and/or $Ca^{2+}-activated$ kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific $K^+$ channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance $K^{+}$ channels (106 pS of chord conductance at +40 mV in physiological $K^+$ gradient). The 106 pS channels were activated by membrane potential and $[Ca^{2+}]_i$, consistent with the known properties of $BK_{Ca}$ channels. $BK_{Ca}$ channels in CRL-1474 were positively regulated by adenylate cyclase activator ($10{\mu}M$ forskolin), 8-Br-cyclic AMP ($300{\mu}M$) or 8-Br-cyclic GMP ($300{\mu}M$). These results suggest that human skin fibroblasts (CR-1474) have typical $BK_{Ca}$ channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

Effects of L-arginine on Endothelium Derived Factors and Cyclic Nucleotides in Broilers under Low Ambient Temperature

  • Han, Bo;Yoon, Soonseek;Han, Hongryul;Wang, Xiaolong
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.11
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    • pp.1570-1574
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    • 2004
  • A flock of AA breed chickens were reared in peterstme brood-vait chamber and were provided with high energy pelleted feed. At 14 d of age, a total of 350 birds were randomly divided into 3 groups as follows: 100 birds were exposed to normal ambient temperature of 20$^{\circ}C$ for control group; 150 birds were exposed to lower ambient temperature of 11$^{\circ}C$ to induce ascites (treatment I); and another group of 100 birds were exposed to lower ambient temperature of 11$^{\circ}C$ and fed diet containing 1% L-arginine for ascitic prophylactic treatment (treatment II). Samples were collected from blood and abdominal fluid of chicken at 3, 4, 5, 6 and 7 wk of age subsequently, to analysis the contents of plasma endothelin (ET-1), angiotensin II (Ang II), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP). The results indicated that the contents of cAMP, cGMP, and Ang II in reatment I and ascitic broilers were higher than the corresponding control group (p<0.01, p<0.05), ET-1 of preascitic broilers were control group (p<0.05), while there was an insignificant difference with later ascitic broilers. The contents of cAMP and cGMP in treatment II were higher than the treatment I and control groups (p<0.01, p<0.05), whereas, the contents of Ang II were gradually decreased compared to the control group (p<0.05), the contents of ET-1 were insignificantly different. On further analysis, the increased plasma Ang II at low ambient temperature condition in broilers made endothelium cell secretion of increased ET-1, cAMP, cGMP and decreased NO. Therefore, low temperature accelerated ascites syndrome in broilers. Supplemently L-arginine can decrease ET-1, and increase cAMP and cGMP. It is concluded that cAMP mediated in broilers pulmonary hypertension syndrome.

Voltammetric Studies of Guanine and Its Derivatives by (TEX)$Ru(bpy)^{2+/3+}$(/TEX) Mediator on Indium Tin Oxide Electrode

  • Kim, Jin Hyeong
    • Bulletin of the Korean Chemical Society
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    • v.21 no.7
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    • pp.709-711
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    • 2000
  • Oxidizing metal complex mediates the electrochemical oxidation of guanine nucleotides. This catalysis results in an enhancement in cyclic voltammograms that yield the rate constant for the oxidation of guanine by the metal complex via digital simulation. The rate constant of oxidation of guanine by Ru(bpy)3(3+) is 6.4 x 10(5)M(-1)s(-l). The rate constant and the enhanced current depend on the number of phosphate groups on the sugar of nucleotidc. Also the modified guanine bases show different oxidation rate constants following the trend guanine-5'- monophosphatc (GMP) > 8-bromo-guanine-5'-monophosphate (8-Br-GMP) > xanthosine -5'-monophosphate (XMP) > inosinc-5'-monophosphate (IMP). The guanine bases derivatized differently are all distinguishable from one another, providing a basis for studying electrochemistry of DNA and RNA and developing electrochemical biosensors.

Inhibitory Effects of Euchrestaflavone B on Thrombus Formation via Regulation of Cyclic Nucleotides in Collagen-induced Platelets (콜라겐 유도의 혈소판에서 사이클릭 뉴클레오티드의 조절을 통한 Euchrestaflavone B의 혈전 형성 억제 효과)

  • Kwon, Hyuk-Woo
    • Korean Journal of Pharmacognosy
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    • v.51 no.4
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    • pp.231-237
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    • 2020
  • Euchrestaflavanone B (EFB) is a flavonoid that can be found in root bark, particularly in Cudrania tricuspidata (C. tricuspidata). The extract of C. tricuspidata is widespread throughout Asia and used in traditional medicine. In a previous study, we found anti-platelet effects of substances isolated from C. tricuspidata on collagen-induced human platelets. However, the C. tricuspidata still contains numerous substances, thus, we have searched new candidate, EFB isolated from C. tricuspidata for anti-platelet effect. Our results showed that EFA inhibited collagen-induced platelet aggregation and glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production and clot retraction. These results suggest that EFA has inhibitory effects on human platelet activities and thrombus formation and has potential value as a natural substance for preventing platelet-induced thrombosis.

The inhibitory effects of glabridin on human platelet aggregation and thrombus formation

  • Sang-Nam Park;Hyuk-Woo Kwon
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.455-461
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    • 2023
  • Glycyrrhiza glabra is a well-known medicinal herb that grows in various parts of the world and glabridin is a major chemical compound that is found in the root extract of Glycyrrhiza glabra. Glabridin is a natural compound known to have antioxidant, anti-inflammatory, anti-atherogenic, anti-osteoporotic and skin-whitening. In this study, we investigated if glabridin inhibited platelet aggregation and thrombus formation. We observed that glabridin inhibited collagen-induced platelet aggregation and suppressed signal transduction molecules such as phosphatidylinositol-3 kinase (PI3K), Akt, glycogen synthase kinase-3α/β (GSK-3α/β), SYK, cytosolic phospholipase A2, and p38 expression. In addition, glabridin suppressed thromboxane A2 generation and thrombin-induced clot retraction. Taken together, glabridin showed strong antiplatelet effects and may be used to block thrombosis- and platelet-mediated cardiovascular diseases.

Inhibitory effects of artemether on thrombus formation via regulation of cyclic nucleotides in collagen-induced platelets (콜라겐-유도의 혈소판에서 사이클릭 뉴클레오티드의 조절을 통한 Artemether의 항혈전 효과)

  • Chang-Eun Park;Dong-Ha Lee
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.239-245
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    • 2022
  • Although normal activation of platelets is important in the process of hemostasis, excessive or abnormal activation of platelets can lead to cardiovascular diseases. Therefore, the discovery of novel substances capable of regulating or inhibiting platelet activation may be helpful in the prevention and treatment of cardiovascular diseases. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. This study investigated the effects of artemether on platelet activation and thrombus formation induced by collagen. As a result, cAMP level was significantly increased by artemether, and VASP and IP3R, substrates of cAMP-dependent kinase, were phosphorylated. IP3R phosphorylation by Artemether inhibited Ca2+ recruitment into the cytoplasm, and phosphorylated VASP inhibited fibrinogen binding by inactivating αIIb/β3 located on the platelet membrane. Consequently, artemether inhibited thrombin-induced fibrin clot formation. Therefore, we propose that artemether can act as an effective prophylactic and therapeutic agent for cardiovascular diseases caused by excessive platelet activation and thrombus formation.

Inhibitory effects of total saponin from Korean red ginseng via vasodilator-stimulated phosphoprotein-Ser157 phosphorylation on thrombin-induced platelet aggregation

  • Lee, Dong-Ha;Cho, Hyun-Jeong;Kim, Hyun-Hong;Rhee, Man Hee;Ryu, Jin-Hyeob;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • v.37 no.2
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    • pp.176-186
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    • 2013
  • In this study, we have investigated the effects of total saponin from Korean red ginseng (TSKRG) on thrombin-induced platelet aggregation. TSKRG dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of about 81.1 ${\mu}g/mL$. In addition, TSKRG dose-dependently decreased thrombin-elevated the level of cytosolic-free $Ca^{2+}$ ($[Ca^{2+}]_i$), one of aggregation-inducing molecules. Of two $Ca^{2+}$-antagonistic cyclic nucleotides as aggregation-inhibiting molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), TSKRG significantly dose-dependently elevated intracellular level of cAMP, but not cGMP. In addition, TSKRG dose-dependently inhibited thrombin-elevated adenosine triphosphate (ATP) release from platelets. These results suggest that the suppression of $[Ca^{2+}]_i$ elevation, and of ATP release by TSKRG are associated with upregulation of cAMP. TSKRG elevated the phosphorylation of vasodilator-stimulated phosphoprotein (VASP)-$Ser^{157}$, a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-$Ser^{239}$, a cGMP-dependent protein kinase substrate, in thrombin-activated platelets. We demonstrate that TSKRG involves in increase of cAMP level and subsequent elevation of VASP-$Ser^{157}$ phosphorylation through A-kinase activation to inhibit $[Ca^{2+}]_i$ mobilization and ATP release in thrombin-induced platelet aggregation. These results strongly indicate that TSKRG is a beneficial herbal substance elevating cAMP level in thrombin-platelet interaction, which may result in preventing of platelet aggregation-mediated thrombotic diseases.

Inhibitory effects of total saponin from Korean Red Ginseng on [Ca2+]i mobilization through phosphorylation of cyclic adenosine monophosphate-dependent protein kinase catalytic subunit and inositol 1,4,5-trisphosphate receptor type I in human platelets

  • Shin, Jung-Hae;Kwon, Hyuk-Woo;Cho, Hyun-Jeong;Rhee, Man Hee;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • v.39 no.4
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    • pp.354-364
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    • 2015
  • Background: Intracellular $Ca^{2+}$($[Ca^{2+}]_i$) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of $[Ca^{2+}]_i$mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the $Ca^{2+}$-antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS). Methods: We investigated the $Ca^{2+}$-antagonistic effect of KRG-TS on cyclic nucleotides-associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I ($IP_3RI$) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation. Results: The inhibition of $[Ca^{2+}]_i$ mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-BrcAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)- dependent protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) ($Thr^{197}$) by KRG-TS. The phosphorylation of $IP_3RI$ ($Ser^{1756}$) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-BrcGMPS. These results suggest that the inhibitory effect of $[Ca^{2+}]_i$ mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation. Conclusion: These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits $[Ca^{2+}]_i$ mobilization in thrombin-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease.