• Title/Summary/Keyword: 5'-GMP production

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Anti-platelet Effects of Dimethyl Sulfoxide via Down-regulation of COX-1 and $TXA_2$ Synthase Activity in Rat Platelets

  • Ro, Ju-Ye;Lee, Hui-Jin;Ryu, Jin-Hyeob;Park, Hwa-Jin;Cho, Hyun-Jeong
    • Biomedical Science Letters
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    • v.20 no.2
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    • pp.70-76
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    • 2014
  • In this study, we investigated the effect of DMSO, a highly dipolar organic liquid, in collagen ($5{\mu}g/ml$)-stimulated platelet aggregation. DMSO inhibited platelet aggregation at 0.5% by inhibiting production of thromboxane $A_2$ ($TXA_2$) which was associated with blocking cyclooxygenase (COX)-1 activity and $TXA_2$ synthase. In addition, DMSO significantly increased the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). On the other hand, DMSO (0.1~0.5% concentration) did not affect the LDH release which indicates the cytotoxicity. Based on these results, DMSO has anti-platelet effect by regulation of several platelet signaling pathways, therefore we suggest that DMSO could be a novel strategy on many thrombotic disorders.

Screening of Potential Compounds Promoting BDNF Production in Noradrenergic Locus Coeruleus Neurons (노르아드레날린성 신경세포에서의 BDNF 생산 증진 물질 탐색)

  • 전홍성
    • KSBB Journal
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    • v.18 no.3
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    • pp.207-210
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    • 2003
  • The locus coeruleus (LC) contains about half of the total number of noradrenergic neurons in the brain and those noradrenergic neurons from the LC innervate entire brain regions. The LC is a major common target region in several neurodegenerative disorders such as Alzheimer's, Pakinson's and Huntington's diseases. The brain-derived neurotrophic factor (BDNF) regulate neuronal cell survival and differentiation of central nervous system neurons, including LC noradrenergic neurons. In this study, various small molecules and growth factors were tested as candidates to promote the production of BDNF in LC noradrenergic neuronal cells. The molecules tested include neuropeptides, cytokines, growth factors, neurotransmitters, and intracellular signaling agents. Four small molecules or growth factors, FGF8b, BMP-4, forskolin, and dibutyryl cGMP, were found to increase the release of BDNF in LC noradrenergic neurons. Especially, BMP-4 significantly enhanced BDNF production over 2.5-fold in LC noradrenergic neurons.

Altered Regulation of Renal Nitric Oxide and Atrial Natriuretic Peptide Systems in Lipopolysaccharide-induced Kidney Injury

  • Bae, Eun-Hui;Kim, In-Jin;Ma, Seong-Kwon;Lee, Jong-Un;Kim, Soo-Wan
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.5
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    • pp.273-277
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    • 2011
  • Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

HACCP in Changran Jeotgal

  • Park Mi-Yeon;Choi Seung-Tae;Chang Dong-Suck
    • Fisheries and Aquatic Sciences
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    • v.5 no.1
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    • pp.48-53
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    • 2002
  • The HACCP (hazard analysis critical control point) concept becomes an important aspect of Good Manufacturing Practices (GMP) in safe food production. The HACCP plan was developed with food safety objective. The authors already carried out hazards analysis on Changran Jeotgal manufacturing process in a previous report. In this study we developed a HACCP plan on the manufacturing process of Changran Jeotgal. We could decide two CCPs those were salt concentration and eliminations of foreign materials before packaging. Foreign materials should be certainly checked out with laser detector just before packaging. Salt should be maintained more than $8\%$ to inhibit pathogenic bacteria in end product. On the Jeotgal process free water is removed after salting and Jeotgal is seasoned with several subsidiary materials such as com syrup. In result end products have $8\%$ salt with water activity 0.82. Most bacteria are inhibited but some can live in this condition. Materials on the working may be contaminate by pathogens, chemicals or physical hazards. It will be decreased by SSOP (standard sanitary operating program). The SSOP needed in Jeotgal plants is nearly same as other general food manufacturing plants but essential to fulfill HACCP program.

Inhibitory effects of isoscopoletin on thrombus formation via regulation of cyclic nucleotides in collagen-induced platelets

  • Lee, Dong-Ha
    • Journal of Applied Biological Chemistry
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    • v.63 no.3
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    • pp.235-241
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    • 2020
  • An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP3R by isoscopoletin induced Ca2+ inhibition from the dense tubular system Ca2+ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β3 in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

Anti-thrombus Effects of Isoscopoletin by Regulating Cyclic Nucleotides on U46619-induced Platelets (U46619 유도의 혈소판에서 Cyclic Nucleotides 조절을 통한 Isoscopoletin의 혈전생성 억제효과)

  • Lee, Dong-Ha
    • Korean Journal of Pharmacognosy
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    • v.52 no.1
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    • pp.26-33
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    • 2021
  • During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

Production of Brewer's Yeast Extract by Enzymatic Method (효소 분해법에 의한 맥주효모 추출물의 제조)

  • 이시경;박경호;백운화;유주현
    • Microbiology and Biotechnology Letters
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    • v.21 no.3
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    • pp.276-280
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    • 1993
  • Cell lytic enzyme, 5'-phosphodiesterase, and AMP-deaminase were used to produce yeast extract as a natural seasoning from beer yeast cells. Prior to the addition of cell lytic enzyme, heat treatment was performed to increase the cell wall degradation` the optimum condition of the cell lytic enzyme was 50C at pH 7.0. The production yields by the enzymatic method and conventional autolysis method were 42% and 35%, respectively. The total quantity of 5'-nucleotides, GMP and IMP, produced by enzymatic method was increased by 45% than that by the conventional method. Futhermore, the operation time of enzymatic method was only 6.5 hrs, significantly reduced from 24 hrs of the conventional method.

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Stimulatory Effect of Ginseng Saponin on Endogenous Production of Nitic Oxide

  • Kim, Hye-Young
    • Proceedings of the Ginseng society Conference
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    • 1998.06a
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    • pp.199-207
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    • 1998
  • Ginseng saponin (G5) purified from Panax ginseng, increase renal blood flow in rats. Nitric oxide (NO) is thought to be a substance endogenously released by G5 in preconstricted lungs and cultured endothelial cells. The present study aims to determine whether G5 could stimulate endogenous 1'elease of NO in rat kidney and urine levels of the stable NO metabolites, nitrite (NO,) and nitrate (NO,) and urinary COMP levels were measured 8 hr after a single intraperitoneal injection of GS (200 mg/kg) Into rats. The effects of the WO synthesis inhibitor, Nu-nitro-L-arginine methyl ester, .1nd the NO precursor, L-arginine, on the G5-induced changes were also determined. The activity of NO synthase, as determined by conversion of ('"C)-L-arginine to ('"C)-L-citrulline, in whole kidney, glomeruli and cortical tubules were also investigated. A single injection of GS resulted in endogenous production of NO as reflected by increase in serum and urine levels of N021N03 and urinary cGMP levels, which were inhibited by the addition o ( N-nitro-L-arginine methyl ester and restored fly L-arginine. GS also stimulated the activity of NO synthase in whole kidney as well as glomeruli and cortical tubules, and Nu-nitro-L-arginine methyl tilter significantly prevented this increase. In conclusion, GS stimulates endogenous NO production and thus, may play a protective role 1 11 the kidney by modulating renal blood flow.

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Study on the Mechanism of Vascular Relaxation Induced by Cortex Caryphylli (정향피 추출물의 혈관 이완효과 및 작용기전에 대한 연구)

  • Song, Chul-Min;Shin, Sun-Ho;Jung, Hyun-Ae;Lee, Jun-Kyoung;Cao, Li-Hua;Kang, Dae-Gil;Lee, Ho-Sup
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1166-1173
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    • 2006
  • The aqueous extracts of Cortex Caryophylli (AEC) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with N$^G$_nitro-L-arginine methyl ester (L-NAME) or 1 H-[1,2,4]-oxadiazole-[4,3-${\alpha}$l-quinoxalin-1-one (ODQ) inhibited the relaxation induced by AEC. AEC-induced vascular relaxations were also markedly attenuated by addition of verapamil, diltiazem and glibenclamide, tetraethylammonium (TEA), respectively, while the relaxation effect of AEC was not blocked by indomethacin, atropine, or propranolol. Moreover, incubation of endothelium-intact aortic rings with AEC increased the production of cGMP. These results suggest that AEC dilates vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling, which seems to be causally related with L-type Ca$^{2+}$ and K$^+$ channels.

Cutting Frequency and Liquid Manure Application on Green Manure Production of Rye and Hairy Vetch in Pear Orchard

  • Lee, Seong Eun;Park, Jin Myeon;Noh, Jae Seung;Lim, Tae Jun;Choi, Dong Geun
    • Korean Journal of Soil Science and Fertilizer
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    • v.46 no.5
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    • pp.322-326
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    • 2013
  • Many organic fruit growers adopt cover cropping in their orchards to improve soil properties. A field experiment was conducted to determine the effects of cutting frequency of cover crop (CF) and liquid manure application (LM) on green manure production (GMP) and returnable nutrient content (RNC) in pear orchard. The combined effects of CF and LM were tested at two levels, respectively, with liquid manure ($L_1$) and without liquid manure ($L_0$). After that, cover crops were cut once ($C_1$) and three times ($C_3$) in rye, and twice ($C_2$) and four times ($C_4$) in hairy vetch. The result showed that main factors related to green manure production were different depending on the species. In rye, LM was more effective in increasing the dry weight of cover crop and RNC than CF. In contrast, the parameters were more affected by CF rather than LM in hairy vetch. Thus, it is suggested that different management technique is needed depending on the cover crop species in order to maximize the green manure production in pear orchard.