• 제목/요약/키워드: Guanosine monophosphate

검색결과 92건 처리시간 0.033초

Ginsenoside Re inhibits pacemaker potentials via adenosine triphosphate-sensitive potassium channels and the cyclic guanosine monophosphate/nitric oxide-dependent pathway in cultured interstitial cells of Cajal from mouse small intestine

  • Hong, Noo Ri;Park, Hyun Soo;Ahn, Tae Seok;Kim, Hyun Jung;Ha, Ki-Tae;Kim, Byung Joo
    • Journal of Ginseng Research
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    • 제39권4호
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    • pp.314-321
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    • 2015
  • Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re ($20-40{\mu}M$) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 50-[${\beta}-thio$]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive $K^{+}$ channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester ($100{\mu}M$), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium ($K^{+}$) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction.

Nucleotide Analysis in Korean Dairy Products Using High- Performance Liquid Chromatography with Diode Array Detector

  • Won, Jong-Eun;Bang, Han-Yeol;Kwak, Byung-Man;Park, Jong-Su;Kim, Gui-Ran;Kwon, Joong-Ho
    • 한국축산식품학회지
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    • 제39권1호
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    • pp.93-101
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    • 2019
  • Nucleotides play important roles in numerous intracellular biochemical processes and are used in infant formulas and other dairy products. However, domestic analytical methods for assessing nucleotide content in products have not yet been established, and therefore, methods for determining nucleotide content are urgently required. A rapid and simple analytical method for determining the content of five types of nucleotides in dairy products was improved using solid phase extraction clean-up and high-performance liquid chromatography with diode array detector. The extraction solvent used in the AOAC method was not well dissolved and was changed to hydrophilic EDTA-Na. In addition, the results obtained using the isocratic elution method and a single wavelength were similar to those obtained using the AOAC method, and the time taken for analysis was shortened from 40 min to 25 min. The process of method validation revealed the following parameters: accuracy (84.69%-102.72%), precision (1.51%-6.82%), linearity (0.999), and limit of detection (cytidine 5'-monophosphate, 0.09 mg/L; uridine 5'-monophosphate, 0.11 mg/L; adenosine 5'-monophosphate, 0.12 mg/L; guanosine 5'-monophosphate, 0.11 mg/L; and inosine 5'-monophosphate, 0.14 mg/L). The method was also used to determine the nucleotide concentration in 25 samples (infant formulas, 1.99-29.39 mg/100 g; and cow milk, 0.28-0.83 mg/100 g). The newly improved method was appropriate for analyzing nucleotides in infant formulas and other dairy products faster when compared to conventional methods.

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

  • 권혁우;신정해;박창은;이동하
    • 대한임상검사과학회지
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    • 제51권1호
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    • pp.34-41
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    • 2019
  • 혈소판 응집은 혈관 손상의 경우 지혈 플러그 형성에 필수적이다. 그러나, 과도한 혈소판 응집은 혈전증, 죽상 동맥 경화증 및 심근 경색과 같은 순환기 장애를 일으킬 수도 있다. Scopoletin은 Scopolia 또는 Artemisia 속 식물의 뿌리에서 발견되는 성분으로, 항응고 및 항말라리아 작용을 가지는 것으로 알려져 있다. 본 연구는 collagen에 의해 유발된 혈소판 응집에 scopoletin이 미치는 영향을 조사하였다. Scopoletin은 활성화된 혈소판에서 생성되는 응집 유도 분자인 thromboxane $A_2$ ($TXA_2$) 및 세포 내 $Ca^{2+}$ 동원 ($[Ca^{2+}]_i$)의 하향 조절을 통해 항 혈소판 효과를 나타내었다. 한편, scopoletin은 세포 내 $Ca^{2+}$-길항제인 것으로 알려져 있는 cyclic adenosine monophosphate(cAMP)와 cyclic guanosine monophosphate (cGMP) 수치를 증가시켰다. 특히, scopoletin은 cGMP보다 cAMP 수준을 강력하게 증가함으로써 콜라겐에 의해 유발된 사람 혈소판 응집에서의 ${\alpha}IIb/{\beta}_3$에 대한 피브리노겐 결합을 억제하였다. 또한, scopoletin은 용량 의존적으로 collagen에 의해 증가된 adenosine trisphosphate (ATP)의 방출을 억제하였다. 이 결과는 혈소판 내 과립 분비를 통한 응집 증폭작용이 scopoletin에 의해 억제되었음을 의미한다. 따라서, 본 연구는 scopoletin이 강력한 항혈소판 효과를 가지며 혈소판-유래의 혈관 질환을 예방할 가능성이 크다는 것을 입증하였다.

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
    • 한국진공학회:학술대회논문집
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    • 한국진공학회 2015년도 제49회 하계 정기학술대회 초록집
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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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Nitric Oxide-cGMP-Protein Kinase G Pathway Contributes to Cardioprotective Effects of ATP-Sensitive $K^+$ Channels in Rat Hearts

  • Cuong, Cang Van;Kim, Na-Ri;Cho, Hee-Cheol;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제8권2호
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    • pp.95-100
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    • 2004
  • Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

쥐를 이용한 포르말린 및 열 유발 통증에서 척수강 Sildenafil의 효과에 관한 연구 (Evaluation for the Effects of Intrathecal Sildenafil on the Formalin- and Thermal-induced Nocieption of Rats)

  • 윤명하;배홍범;신동진;김창모;정성태;김석재;최정일
    • The Korean Journal of Pain
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    • 제19권1호
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    • pp.17-21
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    • 2006
  • Background: Cyclic guanosine monophosphate (cGMP) plays an important role in the modulation of nociception. Although local sildenafil produces antinociception, by increasing cGMP through the inhibition of phosphodiesterase 5, the effect of spinal sildenafil has not been determined. The authors evaluated the effects of intrathecal sildenafil on the nociceptive behavior evoked by formalin injection and thermal stimulation. Methods: Lumbar intrathecal catheters were implanted into rats, with formalin and Hot-Box tests used as nociceptive models. The formalin-induced nociceptive behavior (flinching response) and withdrawal latency to radiant heat were measured, and the general behaviors also observed. Results: The intrathecal administration of sildenafil produced dose-dependent suppression of the flinches in both phases in the formalin test, and increased the withdrawal latency in the Hot-Box test. No abnormal behaviors were noted. Conclusions: Sildenafil, an inhibitor of phosphodiesterase 5, is active against the nociceptive state evoked in the spinal cord by formalin and thermal stimulations. Accordingly, spinal sildenafil may be useful in the management of pain.

In vitro and in vivo evaluation of tissue-cultured mountain ginseng on penile erection

  • Lee, Ho Sung;Lee, Young Joo;Chung, Yoon Hee;Lee, Moo Yeol;Kim, Sung Tae;Ko, Sung Kwon;Momoi, Mariko;Kondoh, Yutaka;Sasaki, Fumio;Jeong, Ji Hoon
    • Journal of Ginseng Research
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    • 제40권4호
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    • pp.334-343
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    • 2016
  • Background: Progressed tissue culture techniques have allowed us to easily obtain mass products of tissue-cultured mountain ginseng over 100 yr old (TCMG-100). We investigated the effects of TCMG-100 extract on erectile function using in vitro and in vivo studies. Methods: To examine the relaxation effects and mechanisms of action of TCMG-100 on rabbit cavernosal strips evaluated in an organ bath. To investigate the long-term treatment effect of TCMG-100, 8-wk administration was performed. After administration of TCMG-100, intracavernosal pressure, cyclic guanosine monophosphate and nitric oxide (NO) levels of cavernosal tissue, serum testosterone level, histological observation of collagen fiber, endothelium, smooth muscle cell, and transforming growth factor-${\beta}1$ were investigated. Results: TCMG-100 extract displayed dose-dependent relaxation effects on precontracted rabbit corporal smooth muscle. The TCMG-100-induced relaxation was significantly reduced by removing the endothelium, and treatment with an NO synthase inhibitor or NO scavenger. Eight weeks of TCMG-100 administration increased intracavernosal pressure in a rat model. The levels of cyclic guanosine monophosphate and NO in the corpus callosum and serum testosterone level were also increased by TCMG-100 treatment. Furthermore, histological evaluation of collagen, smooth muscle, and endothelium showed increases in endothelium and smooth muscle, and a decrease in transforming growth factor-${\beta}1$ expression. Conclusion: These relaxation effects on corporal smooth muscle and increased erectile function suggest that TCMG-100 might be used as an alternative herbal medicine to improve erectile function.

사료 내 Nucleotides 첨가가 참돔P(agrus major)의 성장, 사료효율, 혈액성상 및 비특이적 면역반응에 미치는 영향 (Effects of Dietary Nucleotide Supplementation on the Growth Performance, Feed Utilization, Hematological Parameters and Innate Immunity in Red Seabream Pagrus major)

  • 송진우;이경준
    • 한국수산과학회지
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    • 제46권6호
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    • pp.785-792
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    • 2013
  • Two studies were conducted to investigate the effects of dietary nucleotides (NT) on the growth performance, hematological parameters, and innate immune responses of red seabream Pagrus major. In Expt I, six experimental diets were formulated: a control, four that contained each NT at a level of 0.15% (inosine monophosphate, IMP; adenosine monophosphate, AMP; guanosine monophosphate, GMP; and uridine monophosphate, UMP), and one with a 1:1:1:1 mixture of NTs (IMP, AMP, GMP, and UMP). In Expt II, five experimental diets were formulated that contained 0, 0.1, 0.2, 0.4, and 1.0% IMP (commercial product). Triplicate groups of juvenile (initial body weight 33.1 g) and growing (initial body weight 120 g) red seabream were fed one of the experimental diets to apparent satiation for 8 weeks in Expt I and 12 weeks in Expt II. In Expt I, fish fed diets with NT had higher growth performance than the control group. The nitroblue tetrazolium and lysozyme activities were higher in fish fed the mixed-NT diet, and lowest in the control group. In Expt II, the final body weight and feed utilization of fish fed the 0.1% IMP diet were significantly higher than those of fish fed the control or 1.0% IMP diets. Diet palatability was improved significantly when 0.1% IMP was added. The lysozyme activity was higher in fish fed diets with 0.4-1.0% than in the control group. These results suggest that supplementation of 0.15% IMP and Mixed-NTs in diet can enhance the growth and immune responses in juvenile red seabream. The optimum IMP level appears to be 0.2% in practical feed formulation for growing red seabream.

미생물에 의한 5′-GMP의 생산에 관한 연구 (제1보) XMP-aminase 생산균주의 분리 (Studies on the Fermentative Production of Guanosine -5′-monophosphate by Microorganism (Part 1) Derivation of XMP-aminase Producing Mutants)

  • 배종찬;손충홍;공운영;유주현
    • 한국미생물·생명공학회지
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    • 제7권3호
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    • pp.127-133
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    • 1979
  • 5'-GMP의 직접발효생산균주의 분리목적으로 Breuibacterium ammoniagenes ATCC 6871에 자외선조사 및 NTG, DES 등의 변이제처리를 한 결과 guanine계 핵산관련물질을 직접 배지중에 축적하는 변이주는 분리할 수 없었으며, adenine영양요구주로써 GMP-reductase가 결핍되고 adenosine 및 AMP에 의해 생육저해를 받지 않는 변이주가 XMP-aminase activity가 현저히 높았음을 알았다. 이러한 변이주중 BA-17-2가 XMP-aminase의 activity가 가장 높았으며 또한 전환된 5'-GMP를 GDP나 GTP로 거의 인산화하지 않았으며 그리고 guanosine이나 guanine으로 분해하지 않았다. 생성된 5'-GMP를 anion exchange resin Duolite 102 D를 사용하여 분리하고 ultraviolet 및 Infra-red spectrum을 조사한 결과 5'-GMP로 동정되었다.

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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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    • 제63권3호
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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.