• 대한의생명과학회지
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• 제20권3호
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• pp.129-138
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• 2014

In this study, we investigated the effect of water extract from rice bran (RB) on ADP ($20{\mu}M$)-stimulated platelet aggregation. RB dose-dependently inhibited ADP-induced platelet aggregation, and its $IC_{50}$ value was $224.0{\mu}g/mL$, which was increased by adenylate cyclase inhibitor SQ22536 and cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS. RB elevated the phosphorylation of VASP ($Ser^{157}$) which was also inhibited by SQ22536 and Rp-8-Br-cAMPS. It is thought that RB-elevated cAMP contributed to the phosphorylation of VASP ($Ser^{157}$) to inhibit ADP-induced platelet aggregation. Therefore, we demonstrate that RB has an antiplatelet effect via cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and RB may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• KSBB Journal
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• 제27권5호
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• pp.289-294
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• 2012

Resveratrol, natural polyphenol in grapes and red wine, is known to have the anti-proliferatory and anti-angiogenic effects in various cancer cells. In this study, we have investigated the effects of resveratrol in HT-29 colon cancer cells. Treatment of resveratrol in different concentrations and time inhibited proliferation of HT-29 colon cancer cells. We explored the effects of resveratrol on HT-29 colon cancer cell motility using a wound healing assay. In the absence of the resveratrol, the HT-29 cells are migrated along the edges of the wound and showed a large-scale migration, whereas dose- and time-dependent inhibition of cell flattening and spreading was observed in the presence of resveratrol. Resveratrol inhibited MMP-9 in a dose- and time-dependent on HT-29 colon cancer cells by Western blotting. In addition, resveratrol increased AMPK activity and decreased COX-2, VASP and VEGF expression. Treatment of compound C inhibited AMPK activity, however, the expression of VASP and COX-2 increased thus, COX-2 and VASP are modulated by AMPK. However treatment of celecoxib could not control AMPK activity but decreased VEGF expression. We suggest that resveratrol inhibits cell proliferation and migration through activation of AMPK and decreased COX-2, VASP and VEGF expression in HT-29 colon cancer cells.

• 한국자기학회지
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• 제25권4호
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• pp.101-105
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• 2015

희토류 금속이나 4d/5d 전이금속을 포함하지 않은 3d 전이금속 Fe와 Ni 원소만을 적절하게 배열해도 강한 수직 자기이방성을 가질 수 있음을 예측한 이론 계산 결과가 최근 보고된 바 있다. 그 계산에서는 Fe 층을 표면으로 하는 계만을 고려하였는데 본 논문에서는 Ni가 표면일 때의 자기이방성 에너지를 제일원리계산 방법으로 계산하여 자기이방성을 조절할 수 있는 방안이 있을 수 있는지를 알아 보았다. Fe(001) 표면에 Ni 원소 한 층이 덮였을 때[Ni/Fe(001)]의 자성과 자기이방성을 제일원리계산 방법으로 VASP과 FLAPW 방법을 상호 보완적으로 사용하면서 계산 결과를 비교해 보았다. VASP에 의한 결과는 FLAPW 방법으로 얻은 결과와 큰 차이가 없었고, Fe와 Ni의 강한 띠 혼합으로 Fe와 Ni의 자기모멘트가 모두 증가하였으며 Ni/Fe(001)은 수평 자기이방성을 가지는 것으로 계산되었다. 원자 별 자기이방성 기여도 계산에 의하면 자기이방성에 결정적인 역할을 하는 것은 Ni표면 층임을 알 수 있었다.

• 대한의생명과학회지
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• 제23권3호
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• pp.251-260
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• 2017

Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results, cordycepin increased cAMP and cGMP, which are intracellular $Ca^{2+}$-antagonists. In addition, cordycepin reduced collagen-elevated $[Ca^{2+}]_i$ mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-Br-cAMPS), but not a cGMP-protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). Furthermore, cordycepin increased $IP_3RI$ ($Ser^{1756}$) phosphorylation, indicating inhibition of $IP_3$-mediated $Ca^{2+}$ release from internal store via the $IP_3RI$, which was strongly inhibited by Rp-8-Br-cAMPS, but was not so much inhibited by Rp-8-Br-cGMPS. These results suggest that the reduction of $[Ca^{2+}]_i$ mobilization is caused by the cAMP/A-kinase-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation. In addition, cordycepin increased the phosphorylation of VASP ($Ser^{157}$) known as PKA substrate, but not VASP ($Ser^{239}$) known as PKG substrate. Cordycepin-induced VASP ($Ser^{157}$) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to ${\alpha}IIb/{\beta}_3$, which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of ${\alpha}IIb/{\beta}_3$ activation is caused by the cAMP/A-kinase-dependent VASP ($Ser^{157}$) phosphorylation. In conclusion, these results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of $[Ca^{2+}]_i$ mobilization through cAMP-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation and suppression of ${\alpha}IIb/{\beta}_3$ activation through cAMP-dependent VASP ($Ser^{157}$) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or cardiovascular disease.

• Journal of Nutrition and Health
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• 제41권8호
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• pp.691-700
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• 2008

본 연구는 착상 후 단계의 쥐 배아와 난황낭을 대상으로 구리 결핍이 NO 하부 신호전달체계에 영향을 주는지를 알아보기 위한 것으로, 연구 결과는 다음과 같이 요약할 수 있다. 첫째, 구리 결핍은 정상적인 배아 및 난황낭 발달을 억제하고, NO의 생물학적 이용도와 아세틸콜린에 대한 NO dose-response를 낮추었다. 둘째, 구리 결핍은 NO의 하부 신호전달 물질인 cGMP 수준을 감소시켰으나, NO/cGMP 하부 신호전달체계 표적 중 하나인 P-VASP에는 영향을 미치지 않았다. 셋째, 구리 결핍 배양액에 NO donor를 첨가하는 것은 구리 결핍 배아와 난황낭의 기형 발생 빈도를 구리 정상군과 비슷한 수준으로 개선시켰다. 넷째, NO donor 첨가는 구리 결핍군에서 감소되었던 cGMP의 농도를 유의적으로 증가시켰지만, P-VASP에는 영향을 미치지 않았다. 상기 연구 결과들은 구리 결핍으로 인한 NO의 생물학적 이용도의 감소가 기형발생의 주요 발생 기전이라는 것을 뒷 받침하고 있다. 또한, 임상적으로 임신 기간 중 적절한 구리 섭취의 중요성을 강조한다.

• Journal of Ginseng Research
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• 제40권1호
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• pp.76-85
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• 2016

Background: Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$. Methods: We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$, and clot retraction. Results: KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via phosphorylation of VASP ($Ser^{157}$), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS-increased VASP ($Ser^{157}$) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of ${\alpha}IIb/{\beta}3$ activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of $[Ca^{2+}]_i$ mobilization and increase of cAMP production. Conclusion: These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$, and clot retraction, and may prevent platelet ${\alpha}IIb/{\beta}3$-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS.

• Biomolecules & Therapeutics
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• 제23권1호
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• pp.60-70
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• 2015

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• 대한의생명과학회지
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• 제21권2호
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• pp.103-114
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• 2015

In this study, we investigated the effect of rice bran water extract fermented with Lactobacillus plantarum KCCM-12116 (RBLp) on ADP ($20{\mu}M$)-, collagen ($10{\mu}g/mL$)-, and thrombin (0.2 U/mL)-stimulated platelet aggregation. RBLp dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation, with $IC_{50}$ values of 501.1, 637.2, and > $2,000{\mu}g/mL$, respectively. The platelet aggregation induced by ADP plus RBLp ($750{\mu}g/mL$) was increased by the adenylate cyclase inhibitor, SQ22536, and the cAMP-dependent protein kinase (A-kinase) inhibitor, Rp-8-Br-cAMPS. Treatment with RBLp increased the phosphorylation of VASP ($Ser^{157}$), an A-kinase substrate, which was also inhibited by SQ22536 and Rp-8-Br-cAMPS. It is thought that the RBLp-induced increases in cAMP contributed to the phosphorylation of VASP ($Ser^{157}$), which in turn resulted in an inhibition of ADP-induced platelet aggregation, thereby indicating that RBLp has an antiplatelet effect via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). Thus, RBLp may have therapeutic potential for the treatment (or prevention) of platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• Journal of Electrochemical Science and Technology
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• 제2권3호
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• pp.146-151
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• 2011

The formation of Li-Si-O phases, $Li_4SiO_4$ and $Li_2SiO_3$ from the starting materials SiO and $Li_2O$ are analyzed using Vienna Ab-initio Simulation (VASP) package and the total energies of Li-Si-O compounds are evaluated using Projector Augmented Wave (PAW) method and correlated the structural characteristics of the binary system SiO-$Li_2O$ with experimental data from electrochemical method. Despite $Li_2SiO_3$ becomes stable phase by virtue of lowest formation energy calculated through VASP, the experimental method shows presence of $Li_4SiO_4$ as the only product formed when SiO and $Li_2O$ reacts during slow heating to reach $550^{\circ}C$ and found no evidence for the formation of $Li_2SiO_3$. Also, higher density of $Li_4SiO_4$(2.42 g $ml^{-1}$) compared to the compositional mixture $1SiO_2-2Li_2O$ (2.226 g $ml^{-1}$) and better cycle capacity observed through experiment proves that $Li_4SiO_4$ as the most stable anode supported by better cycleabilityfor lithium ion battery remains as paradox from the point of view of VASP calculations.

• 한국전기전자재료학회논문지
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• 제18권7호
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• pp.589-593
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• 2005

The electronic states of ZnO doped with Al, Ga and In, which belong to III family elements in periodic table, were calculated using the density functional theory. In this study, the calculation was performed by two Programs; the discrete variational Xa (DV-Xa) method, which is a sort of molecular orbital full potential method; Vienna Ab-initio Simulation Package (VASP), which is a sort of pseudo potential method. The fundamental mixed orbital structure in each energy level near the Fermi level was investigated with simple model using DV-Xa. The optimized crystal structures calculated by VASP were compared to the measured structures. The density of state and the energy levels of dopant elements were shown and discussed in association with properties.