• Title/Summary/Keyword: [Ca(2+)]i mobilization

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Inhibitory effect of ethanol extract of Gryllus bimaculatus on platelet aggregation and glycoprotein IIb/IIIa activation (쌍별귀뚜라미 에탄올 추출물의 혈소판응집반응과 당단백질 IIb/IIIa 활성화 억제 효과)

  • Hyuk-Woo Kwon;Man Hee Rhee;Jung-Hae Shin
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.236-243
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    • 2023
  • Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A2 production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A2, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

Total saponin from Korean Red Ginseng inhibits binding of adhesive proteins to glycoprotein IIb/IIIa via phosphorylation of VASP (Ser157) and dephosphorylation of PI3K and Akt

  • Kwon, Hyuk-Woo;Shin, Jung-Hae;Cho, Hyun-Jeong;Rhee, Man Hee;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • v.40 no.1
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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.

Effect of Calcium Chloride and Sodium Chloride on the Leaching Behavior of Heavy Metals in Roadside Sediments (염화칼슘과 소금이 도로변 퇴적물의 중금속 용출에 미치는 영향)

  • Lee Pyeong koo;Yu Youn hee;Yun Sung taek
    • Journal of Soil and Groundwater Environment
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    • v.9 no.4
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    • pp.15-23
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    • 2004
  • Deicer operations provide traffic safety during winter driving conditions in urban areas. Using large quantities of de-icing chemicals (i.e., $CaCl_2$ and NaCl) can cause serious environmental problems and may change behaviors of heavy metals in roadside sediments, resulting in an increase in mobilization of heavy metals due to complexation of heavy metals with chloride ions. To examine effect of de-icing salt concentration on the leaching behaviors and mobility of heavy metals (cadmium, zinc, copper, lead, arsenic, nickel, chromium, cobalt, manganese, and iron), leaching experiments were conducted on roadside sediments collected from Seoul city using de-icing salt solutions having various concentrations (0.01-5.0M). Results indicate that zinc, copper, and manganese in roadside sediments were easily mobilized, whereas chromium and cobalt remain strongly fixed. The zinc, copper and manganese concentrations measured in the leaching experiments were relatively high. De-icing salts can cause a decrease in partitioning between adsorbed (or precipitated) and dissolved metals, resulting in an increase in concentrations of dissolved metals in salt laden snowmelt. As a result, run-off water quality can be degraded. The de-icing salt applied on the road surface also lead to infiltration and contamination of heavy metal to groundwater.

Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway

  • Gao, Quan-Gui;Zhou, Li-Ping;Lee, Vien Hoi-Yi;Chan, Hoi-Yi;Man, Cornelia Wing-Yin;Wong, Man-Sau
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.527-538
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    • 2019
  • Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.