• Journal of Applied Biological Chemistry
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• 제66권
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• pp.221-226
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• 2023

혈소판의 적절한 활성화와 응집이 필요하지만 과도하거나 비정상적인 응집은 뇌졸중, 혈전증, 동맥경화증과 같은 심혈관 질환을 유발할 수 있다. 따라서 이러한 질병을 예방하고 치료하기 위해서는 혈소판 응집을 조절하거나 억제할 수 있는 물질을 찾는 것이 중요하다. 여러 연구에서 Panax 인삼의 특정 ginsenoside 화합물이 혈소판 응집을 억제할 수 있음이 알려져 있다. 이들 화합물 중 Panax ginseng의 Rk3 (G-Rk3)는 혈소판 응집 억제의 기전이 불확실 하기에 이를 밝히기 위한 연구가 필요하다. G-Rk3는 cAMP의 양을 강하게 증가시켰고 cAMP 의존성 kinase의 기질인 VASP 및 IP3R의 인산화를 유도했다. 또한, G-Rk3의 효과는 PI3K/Akt 인산화의 억제를 일으켜 세포 내 과립의 분비를 감소시켰다. 궁극적으로 G-Rk3는 혈소판 응집을 효과적으로 억제하였다. 따라서 우리는 과도한 혈소판 응집으로 인한 심혈관 질환의 예방 또는 치료제로서의 G-Rk3의 가능성을 제안한다.

• 생약학회지
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• 제52권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.647-655
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• 1997

The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.

• Natural Product Sciences
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• 제9권1호
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• pp.44-48
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• 2003

The effect of aqueous extract of Stachys riederi var. japonica Miq. (Labiatae) (SRAE) on the immediate-type allergic reactions was investigated. SRAE was found to exhibit a inhibitory activity on the compound 48/80-induced systemic anaphylaxis in mice. SRAE inhibited the plasma histamine release induced by compound 48/80 in mice. In addition, SRAE also inhibited the passive cutaneous anaphylaxis reaction induced by IgE/anti-IgE in mice. The effect of SRAE on the histamine release from rat peritoneal mast cells (RPMC) was studied. SRAE inhibited the histamine release induced by compound 48/80 in RPMC. To clarify the mechanism of these inhibiting reactions, we investigated the effects of SRAE on cyclic AMP (cAMP). The level of cAMP in human leukemia cell line, HMC-1, when SRAE (1 mg/ml) was added, significantly increased compared with that of basal cells. These results indicate that SRAE may be beneficial in the treatment of immediate-type allergic reaction.

• 통합자연과학논문집
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• 제4권3호
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• pp.222-226
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• 2011

Cyclic AMP receptor protein(CRP) is involved in the activation of many genes corresponding to catabolite enzymes in Escherichia coli. In this study, mutant CRP(S128A) was used to elucidate the effect of Ser 128 on the cAMP-induced structural change. Based on the protease digestion and thermal analysis, serine 128 in CRP affects the cAMP binding capability and then structural change of CRP protein. In addition, CD spectra in near UV region revealed that S128A CRP retained the sensitive conformation to thermal effect relative to that of wild-type CRP, in spite of identical Tm values in the absence of cAMP.

• Molecules and Cells
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• 제26권1호
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• pp.87-92
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• 2008

We employed dual color Fluorescence Cross Correlation Spectroscopy (FCCS) to measure the interaction between PKA regulatory (RII) and catalytic subunits (CAT) in living cells. Elevation of intracellular cAMP with forskolin decreased the cross-correlation amplitude between RFP-fused RII (RII -mRFP) and GFP-fused CAT (CAT-EGFP) by 50%, indicating that cAMP elevation leads to dissociation of RII-CAT complexes. Moreover, diffusion coefficient analysis showed that the diffusion rate of CAT-EGFP was significantly increased, suggesting that the decreased RII-CAT association caused by cAMP generated free CAT subunits. Our study demonstrates that in vivo FCCS measurements and their quantitative analysis permit one not only to directly quantify protein-protein interactions but also to estimate changes in the intracellular cAMP concentration.

• Journal of Ginseng Research
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• 제37권2호
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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.

• 미생물학회지
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• 제24권2호
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• pp.194-197
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• 1986

Malonate kinase and isocitrate lyase were induced in Acinetobacter calcoaceticus grown on malonate as a sole carbon source but repressed by succinate. The induction of those two enzymes was stimulated by dibutyryl cyclic adenosine 3', 5'-monophosphate, indicating that the expression of their genes for those enzymes is dependent on cyclic adenosine 3', 5'-monophosphate.

• 한국정보디스플레이학회:학술대회논문집
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• 한국정보디스플레이학회 2009년도 9th International Meeting on Information Display
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• pp.1578-1581
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• 2009

This work describes a power and area efficient switched-capacitor cyclic DAC for mobile display drivers. The proposed DAC can be simply implemented with one opamp two capacitors and several switches. Furthermore, the op-amp input referred offset is attenuated at the DAC output without additional offset cancellation circuitry. The operation of the cyclic DAC is verified through circuit level simulations.

• 생명과학회지
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• 제10권3호
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• pp.279-285
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• 2000

cAMP 수용성 단백질인 CRP는 Escherichia coli에서 대사와 관련된 유전자의 전사를 조절한다. 본 연구는 야생형과 돌연변이 CRP 단백질의 열적 안정성과 온도에 따른 단백질의 구조변화를 관찰하기 위 하여 proteolytic digestion, UV spectrophotometer, CD spectrapolarimeter 등의 방법을 사용하였다. cAMP가 없을 때에는 야생형, S83G, S128A CRP가 열적 안정성에서 큰 차이를 보이지 않았지만, cAMP가 존재할 때 야생형 CRP가 다른 돌연변이 CRP보다 열적으로 더욱 안정함을 보였다. 그리고 protease digestion 실험을 통하여 높은 온도에서 cAMP의 존재와 무관하게 돌연변이 CRP에서 단백질 의 변성으로 인한 절단된 단백질띠를 관찰할 수 있었다. 그리고 55$^{\circ}C$에서 측정한 CD 스펙트럼에서 단백 질의 2차 구조인 $\alpha$-helix 구조가 부분적으로 파괴되었음이 관찰되었다.