• Title/Summary/Keyword: cGMP production

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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.

Inhibitory Effects of Scopoletin in Collagen-induced Human Platelet Aggregation (콜라겐으로 유도한 사람 혈소판 응집에 미치는 Scopoletin의 억제 효과)

  • Kwon, Hyuk-Woo;Shin, Jung-Hae;Park, Chang-Eun;Lee, Dong-Ha
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.1
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    • pp.34-41
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    • 2019
  • Platelet aggregation is essential for the formation of a hemostatic plug in the case of blood vessel damage. On the other hand, excessive platelet aggregation may cause cardiovascular disorders, such as thrombosis, atherosclerosis, and myocardial infarction. Scopoletin, which found in the root of plants in the genus Scopolia or Artemisia, has anti-coagulation and anti-malaria effects. This study examined the effects of scopoletin on human platelet aggregation induced by collagen. Scopoletin had anti-platelet effects via the down-regulation of thromboxane $A_2$ ($TXA_2$) production and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), which are aggregation-inducing molecules produced in activated platelets. On the other hand, scopoletin increased both the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels, which are known as intracellular $Ca^{2+}$-antagonists and aggregation-inhibiting molecules. In particular, scopoletin increased the potently cAMP level more than cGMP, which led to suppressed fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in collagen-induced human platelet aggregation. In addition, scopoletin inhibited collagen-elevated adenosine triphosphate (ATP) release in a dose-dependent manner. The results suggest that aggregation amplification through granule secretion is inhibited by scopoletin. Therefore, scopoletin has potent anti-platelet effects and may have potential for the prevention of platelet-derived vascular diseases.

Anti-Anaphylactic Effects of Natural Extract Compounds(AllerQ) in the Rats (천연물 복합체가 추출물(알러큐)의 알러지 유발 흰쥐에 대한 항알러지 효과)

  • Suh Kyong-Suk;Kwon Myung-Sang;Cho Jung-Soon
    • Journal of the East Asian Society of Dietary Life
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    • v.14 no.5
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    • pp.425-437
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    • 2004
  • Medicinal plants are of great importance in providing healthcare to a large portion of the population in Korea. A number of plants are described in Dong-Ui-Bo-Gam for use in the treatment of allergic disorders, namely psoriasis, eczema, bronchial asthma, etc. In this study, we evaluated the effect of AllerQ, which is multi-complexes of various plants extracts such like Mori folium, Scutellaria baicallensis, Glycyrrhiza uralnsis, Mentha sacharinensis and Poncirus trifoliata on compound 48/80 induced anaphylactic shock, ovalbumin induced asthma in vivo and anti-IgE antibody induced hypersensitivity in vitro. We found antianaphylactic or antiallergic properties of AllerQ when given orally. AllerQ for prophylactic treatment for anaphylactic shocks have produced good results. AllerQ may modulate various aspects of immune function and allergic inflammation. In the present study, we analyse the effects of AllerQ on mast cell degranulation, mortality, cAMP/cGMP, O₂, H₂O₂ level, cyokine production and on the elicitation of IgE-mediated mast cell-dependent allergic inflammation in vivo and in vitro. We have established that AllerQ inhibited histamine release, cAMP/cGMP, O₂, H₂O₂ level, IL-4, tumor necrosis factor-alpha(TNF-α) and IL-6 production without having any significant physical change. These effects have been observed in mast cell(in vitro) and serum(in vivo) derived from three different origins that were activated by either immunological or non-immunological stimuli. These results suggest that the antianaphylactic and antiasthma tic action of AllerQ may be associated with an increase in the intracellular inhibition of the cAMP phosphodiesterase. Furthermore, AllerQ identified as potent inhibitors on O₂, H₂O₂ and cytokine activity. these data suggest that AllerQ may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as an useful functional food.

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Role of Exogenous Nitric Oxide Generated through Microwave Plasma Activate the Oxidative Signaling Components in Differentiation of Myoblast cells into Myotube

  • Kumar, Naresh;Shaw, Priyanka;Attri, Pankaj;Uhm, Han Sup;Choi, Eun Ha
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.158-158
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    • 2015
  • Myoblast are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of skeletal muscle; The neuronal isoform of nitric oxide synthase (nNOS, termed also NOS-I) is expressed in normal adult skeletal muscle, suggesting important functions for Nitric oxide (NO) in muscle biology1,2,3. However, the expression and subcellular localization of NO in muscle development and myoblast differentiation are largely unknown. In this study, we examined effects of the nitric oxide generated by a microwave plasma torch, on proliferation/differentiation of rat myoblastic L6 cells. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimetres per minute. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the ratio of oxygen gas, and the microwave power4. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to L6 skeletal muscles. Differentiation of L6 cells into myotubes was significantly enhanced the differentiation after nitric oxide treatment. Nitric oxide treatment also increase the expression of myogenesis marker proteins and mRNA level, such as myogenin and myosin heavy chain (MHC), as well as cyclic guanosine monophosphate (cGMP), However during the myotube differentiation we found that NO activate oxidative stress signaling erks expression. Therefore, these results establish a role of NO and cGMP in regulating myoblast differentiation and elucidate their mechanism of action, providing a direct link with oxidative stress signalling, which is a key player in myogenesis. Based on these findings, nitric oxide generated by plasma can be used as a possible activator of cell differentiation and tissue regeneration.

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Mechanism for the Vascular Relaxation Induced by Butanol Extract of Agrimonia pilosa (선학초 부탄올 추출물의 혈관 이완 효과의 기전에 대한 연구)

  • Hua, Cao-Li;Lee, Jun-Kyung;Cho, Kuk-Hyun;Kwon, Tae-Oh;Kwon, Ji-Woong;Kim, Jin-Sook;Sohn, Eun-Jin;Lee, Ho-Sub;Kang, Dae-Gill
    • Korean Journal of Pharmacognosy
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    • v.37 no.2 s.145
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    • pp.67-73
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    • 2006
  • The butanol extracts of Agrimonia pilosa (BAP) induced dose-dependent vascular 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) and 1H-[1,2,4]-oxadiazole-[$4,3-{\alpha}$]-quinoxalin-1-one(ODQ) inhibited the relaxation induced by BAP. BAP-induced vascular relaxation was also markedly attenuated by addition of verapamiI, while the relaxant effect of BAP was not blocked by indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolo. In addition, incubation of endothelium-intact aortic rings with BAP increased the vascular production of cGMP. These results suggest that BAP relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling pathway, which may be causally related with L-type $Ca^{2+}$ channels.

Effect of Lophatherum gracile on the mechanism of vasorelaxation in thoracic aorta (담죽엽 추출물의 혈관이완 기전에 대한 연구)

  • Kim, Hye-Yoom;Li, Xiang;Lee, Yun-Jeong;Seo, Hwan-Ho;Cho, Nam-Geun;Kang, Dae-Gill;Lee, Ho-Sub
    • Herbal Formula Science
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    • v.17 no.2
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    • pp.175-186
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    • 2009
  • The vasorelaxant effect of an extract of Lophatherum gracile Brongn (ELB) and its possible action mechanism were ascertained in aortic tissues isolated from rats. ELB relaxed endothelium-intact thoracic aorta in a dose-dependent manner. However, the induced vascular relaxation was abolished by removal in endothelium of the thoracic aorta. Pretreatment of endothelium-intact vascular tissues with $N^G$-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-$\alpha$]-quinoxalin-1-one (ODQ) significantly inhibited vascular relaxation induced by ELB. Moreover, ELB significantly increased cGMP production in aortic tissues, which was blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of ELB was attenuated by tetraethylammonium (TEA), and glibenclamide. ELB-induced vasorelaxation was not blocked by atropine, propranolol, indomethacin, verapamil, and diltiazem. Taken together, the present study demonstrates that ELB dilates vascular smooth muscle via an endothelium-dependent NO-cGMP signaling pathway, which may be at least in part related with the function of $K^+$ channels.

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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.

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.

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.

Relaxing Effects of Acanthopanacis Cortex through NO Production and PDE-5 Inhibition in Corpus Cavernosum (오가피의 NO 생성과 PDE-5 억제를 통한 음경해면체 이완효과)

  • Kim, Ho Hyun;Park, Sun Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.1
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    • pp.52-58
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    • 2017
  • This study was aimed to examine relaxing effects of Acanthopanacis cortex(AC) through nitric oxide(NO) production and phosphodiesterase type 5(PDE-5) inhibition in corpus cavernosum. In order to define the relaxation effects of AC extract, rabbit corpus cavernous tissues were prepared in $2{\times}2{\times}8mm$ sized strip. AC extract ($0.01-3.0mg/m{\ell}$) were treated in contracted strips induced by phenylephrine(PE) and $N{\omega}$-nitro-L-arginine (L-NNA) was treated before AC extract-treated. And calcium chloride($Ca^{2+}$) 1 mM was infused into precontracted strips after pretreatment of AC extract in $Ca^{2+}-free$ krebs-ringer solution. When AC extract was applied to human umbilical vein endothelial cell(HUVEC), cell viability was measured by MTT assay, and NO concentration was measured by Griess reagent system. Ratio of smooth muscles to collagen fibers and eNOS, PDE-5 positive reaction were measured by histochemical and immunohistochemical process on mice corpus cavernosum. AC extract significantly affected relaxion of the cavernous strips, and the pretreatment of L-NNA inhibited AC extract-induced relaxation. Contraction induced by the addition of $Ca^{2+}$ was inhibited by treatment with the AC extract in $Ca^{2+}-free$ solution. In AC group, NO concentration, ratio of smooth muscle to collagen fibers, and eNOS positive reaction were increased, PDE-5 positive reaction was decreased compared to PE group. As a result of the above experiment, it was thought that AC extract inhibits the inflow of extracellular $Ca^{2+}$ by activating cGMP through the increase of eNOS / NO and the decrease of PDE-5 which inhibits cGMP activity, in the corpus cavernosum.