• Title/Summary/Keyword: Calcium signal

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The inhibitory activity of ginsenoside Rp4 in adenosine diphosphate-induced platelet aggregation

  • Son, Young-Min;Jeong, Da-Hye;Park, Hwa-Jin;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.96-102
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    • 2017
  • Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

The Study of in Vivo Visual Pathway Tracing using Magnetic Magnanese Tracer (자성 망간 추적자를 이용한 in Vivo 시신경경로 추적에 관한 연구)

  • Bae, Sung-Jin;Chang, Yong-Min
    • Progress in Medical Physics
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    • v.18 no.1
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    • pp.42-47
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    • 2007
  • Purpose: To evaluate the tracing of optic nerve tract using manganese enhanced magnetic resonance Imaging. Materials and Methods: After injecting $30{\mu}l$ of $MnCl_2(1mol)$ (1 mol) Into the retina of female New Zealand white rabbit, the contrast enhancements at major anatomical structures of optic nerve tract were evaluated by high resolution T1-weighted Images 12 hours, 24 hours, and 48 hours after $MnCl_2(1mol)$ Injection using 3D FSPGR (Fast Speiled Gradient Recalled echo) pulse sequence at 1.5T clinical MR scanner with high performance gradient system. Also, for quantitative evaluation, the signal-to-noise ratios of circular ROI on anatomical locations were measured. Results: The major structures on the optic nerve tract were enhanced after injecting $MnCl_2(1mol)$. The structures, which showed enhancement, were right optic nerve, optic chiasm, left optic tract, left lateral geniculate nucleus, left superior colliculus. The structures on the contralateral optic pathway to the right retina were enhanced whereas the structures on the ipsilateral pathway did not show enhancement. Conclusion: The Mn transport through axonal pathway of optic nerve sys)em was non- invasively observed after injecting injecting $MnCl_2$ at the retina, which is the end terminal of optic nerve system. This Mn transport seems to occur by voltage gated calcium $(Ca^{2+})$ channel and In case of direct Injection Into the retina, the fast transpori pathway of voltage gated calcium channel seems to be responsible for Mn transport.

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Cell death phenotype of vacuole Ca2+-ATPase11 (ACA11) transgenic plant in Arabidopsis (애기장대에서 액포막 존재 Ca2+-ATPase11 (ACA11) 형질전환제의 세포사멸 표현형 분석)

  • Lee, Sang-Min;Hoang, My-HanhThi;Kim, Kyung-Eun;Chung, Woo-Sik
    • Journal of Plant Biotechnology
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    • v.36 no.1
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    • pp.59-63
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    • 2009
  • Calcium ion ($Ca^{2+}$) is thought to play the important role as a second messenger for signal transduction that results in various physiological responses to cope with developmental programs and environmental changes in plant. In plant cells, the central vacuole functions as a major calcium store, which is important for both signal transduction and preventing cytotoxicity. Although there is evidence for the biochemical characterizations of a calmodulin-regulated $Ca^{2+}$-ATPase (ACA11) localized to vacuole membrane, the biological function to ACA11 in plant has not been verified. In this study, we show that the cell death as the hypersensitive response (HR) in mature leaves is induced in transgenic plant of a vacuole ACA-type $Ca^{2+}$-ATPase, ACA11. Evidence that cell death phenotype is the result of ACA11 gene silencing is provided by Western blot assay using membrane fraction proteins extracted from transgenic plant. The 3, 3'-diaminobenzidine (DAB) staining study provides that the cell death is caused by the increase of reactive oxygen species (ROS) in mature leaves of transgenic plants.

Inhibitory Effect of Dendrobium moniliforme on Degranulation and Histidine Decarboxylase Expression in RBL-2H3 Cells (RBL-2H3 세포에서 탈과립과 histidine decarboxylase 발현에 미치는 석곡(Dendrobium monilifrme)의 효과)

  • Young Ji Lee;Iskander Madhi;YoungHee Kim
    • Journal of Life Science
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    • v.33 no.2
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    • pp.176-182
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    • 2023
  • The stems of Dendrobium moniliforme are used in traditional Oriental medicine as a Yin tonic to nourish the stomach, promote the production of body fluid, and reduce fever. This study investigated the effects of the aqueous extract of D. moniliforme stems (DME) on mast cell degranulation and the expression of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and histamine-synthesizing enzyme histidine decarboxylase (HDC). We used rat mast cell line RBL-2H3 cells and stimulated them with PMA plus calcium ionophore (PMACI). Pretreatment with DME significantly inhibited PMACI-induced β-hexosaminidase release and the expression of TNF-α, IL-4, and HDC. Furthermore, DME suppressed PMACI-induced nuclear translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). In addition, HDC expression was inhibited by SP600125 (JNK inhibitor), PD98059 (ERK inhibitor), and SB203580 (p38 kinase inhibitor). Finally, the phosphorylation of p38 kinase, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) was inhibited by pretreatment with DME. These results suggest that DME has inhibitory effects against degranulation, cytokine (TNF-α and IL-4) and HDC expression, and that HDC expression is mediated by MAPK signaling. These findings suggest that DME may have therapeutic potential in the treatment of hypersensitive and inflammatory diseases.

Pathophysiology and MRI Findings of Infectious Spondylitis and the Differential Diagnosis (감염성 척추염과 감별질환의 병태생리와 MRI 소견)

  • Sunjin Ryu;Yeo Ju Kim;Seunghun Lee;Jeongah Ryu;Sunghoon Park;Jung Ui Hong
    • Journal of the Korean Society of Radiology
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    • v.82 no.6
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    • pp.1413-1440
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    • 2021
  • On MRI, abnormal signals of the intervertebral disc, destruction of the upper and lower vertebral body endplate around the disc, and bone marrow edema around the endplate are considered typical findings of infectious spondylitis. These findings can also appear in various non-infectious spinal diseases, such as degenerative changes, acute Schmorl's node, spondyloarthropathy, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO), chronic recurrent multifocal osteomyelitis, and calcium pyrophosphate dihydrate crystal deposition disease. The imaging findings of infectious spondylitis that can be differentiated from these non-infectious spinal diseases on MRI are high signal intensity and abscess of the disc space, an abscess in the paraspinal soft tissue, and the loss of the linear low signal intensity on T1-weighted images of the bony endplate. However, these differentiation points do not always apply since there are many similarities in the imaging findings of infectious and non-infectious diseases. Therefore, for an accurate diagnosis, it is important to know the imaging characteristics related to the pathophysiology of not only infectious spondylitis but also non-infectious spinal diseases, which requires differentiation from infection.

Short Heterodimer Partner as a Regulator in OxLDL-induced Signaling Pathway

  • Kimpak, Young-Mi
    • Proceedings of the PSK Conference
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    • 2001.10a
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    • pp.109-113
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    • 2001
  • Oxidized low-density lipoprotein (oxLDL) has been shown to modulate transactivations by the peroxisome proliferator activated receptor (PPAR)$\gamma$ and nuclear factor-kappa B (NF$\kappa$B). In this study, the oxLDL signaling pathways involved with the NF$\kappa$B transactivation were investigated by utilizing a reporter construct driven by three upstream NF$\kappa$B binding sites, and various pharmacological inhibitors. OxLDL and its constituent lysophophatidylcholine (lysoPC) induced a rapid and transient increase of intracellular calcium and stimulated the NF-KB transactivation in resting RAW264.7 macrophage cells in an oxidation-dependent manner. The NF$\kappa$B activation by oxLDL or lysoPC was inhibited by protein kinase C inhibitors or an intracellular calcium chelator. Tyrosine kinase or PI3 kinase inhibitors did not block the NF$\kappa$B transactivation. Furthermore, the oxLDL-induced NF$\kappa$B activity was abolished by the PPAR$\gamma$ ligands. When the endocytosis of oxLDL was blocked by cytochalasin B, the NF$\kappa$B transactivation by oxLDL was synergistically increased, while PPAR transactivation was blocked. These results suggest that oxLDL activates NF-$\kappa$B in resting macrophages via protein kinase C- and/or calcium-dependent pathways, which does not involve the endocytic processing of oxLDL. The endocytosis-dependent PPAR$\gamma$ activation by oxLDL may function as an inactivation route of the oxLDL induced NF$\kappa$B signal. Short heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA-binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but suppressed by oxLDL and its constituent I3-HODE, a ligand for peroxisome proliferator-activated receptor y. Furthermore, SHP acted as a transcription coactivator of nuclear factor-$\kappa$B (NF$\kappa$B) and was essential for the previously described NF$\kappa$B transactivation by lysoPC, one of the oxLDL constituents. Accordingly, NF$\kappa$B, transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells, as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF$\kappa$B in oxLDL-treated, resting macrophage cells.

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Structure-dependent Mechanism of Action of Poly Aromatic Hydrocarbons in Cultured Primary Hepatocytes (간세포에서 PAH의 구조 의존적 작용기전)

  • Kim Sun-Young;Hong Sung-Bum;Yang Jae-Ho
    • Toxicological Research
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    • v.22 no.1
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    • pp.23-30
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    • 2006
  • Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

Distribution of Taste Receptors in Submandibular and von Ebner Salivary Glands

  • Jun, Yong-Ku;Kim, Se-Nyun;Lee, Cil-Han;Cho, Young-Kyung;Chung, Ki-Myung;Roper, Stephen D.;Kim, Kyung-Nyun
    • International Journal of Oral Biology
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    • v.33 no.1
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    • pp.13-23
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    • 2008
  • Taste is a critically important sense for the survival of an organism. However, structure and distribution of taste receptors were only recently investigated. Although expression of the ion channels responsible for the sense of salty taste and acidity was observed in the non-taste cells, receptors for sweet and bitter taste were only identified in taste cells. Salivary glands are involved in the sensing of taste and plays important roles in the transduction of taste. The purpose of this study is to examine whether taste receptors are present in the salivary glands and to provide clues for the investigation of the taste-salivary glands interaction. Using microarray and RT-PCR analyses, the presence of taste receptor mRNAs in the rat von Ebner gland and submandibular gland was confirmed. Type I taste receptors were preferentially expressed in von Ebner gland, whereas type II taste receptors were expressed in both von Ebner gland and submandibular gland. The tastespecific signal tranducing proteins, $G_{\alpha}gustducin$ and phospholipase C ${\beta}2$, were also detected in both salivary glands by immunohistochemistry. Finally, the activation of the calcium signal in response to bitter taste in the acinar cells was also observed. Taken together, these results suggest that taste receptors are present in the von Ebner gland and submandibular gland and that type II taste receptors are functionally active in both salivary glands.

Double Pulse Raman-Laser Induced Plasma Spectroscopy System for Space Exploration (우주 탐사를 위한 이중펄스 라만-레이저 유도 플라즈마 분광 시스템 개발 연구)

  • Yang, Jun-Ho;Yoh, Jai-Ick
    • Journal of the Korean Society for Aeronautical & Space Sciences
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    • v.48 no.6
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    • pp.479-487
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    • 2020
  • A new double-pulse laser system that combines Raman and laser induced plasma spectroscopy (LIPS) in a single unit is proposed. The study attempts to enhance the laser induced plasma signals while simultaneously extracting the desired molecular signals from Raman spectroscopy. In low pressure conditions such as the lunar atmosphere, the measuring of plasma emission is hard because of the low electron density and short persistence time causing a rapid plasma expansion. Furthermore, in the integration of the detecting system aimed at space exploration, the minimization of laser system is important in terms of the payload mass. Simultaneous molecular and atomic detection that gave highly resolved spectral data at pressure below 0.07 torr is demonstrated amongst eight rock samples test. The plasma stacking produced from the double-pulse laser enhanced the signal intensity of calcium and oxygen lines in calcite matrix by twofold, compared to a conventional LIPS.

Inhibitory Activities of Red Ginseng Acidic Polysaccharide in Platelet Aggregation

  • Lee, Whi-Min;Kamruzzaman, S.M.;Song, Yong-Bum;Cho, Jae-Youl;Park, Hwa-Jin;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.32 no.1
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    • pp.73-78
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    • 2008
  • Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), has been shown to have a variety of biological functions such as immunostimulating and anti-tumor activities. In the present study, we investigated whether RGAP inhibited ligand-induced platelet aggregation. The washed platelet-rich plasma was prepared from male SD rats with successive centrifugation. The platelets $(10^8/ml)$ were preincubated with 1 mM of $CaCl_2$ for 2 min either in the presence or in the absence of RGAP $(10{\sim}50\;{\mu}g/ml)$ and were stimulated with collagen (2.5 ${\mu}g/ml$) and thrombin (0.1 U/ml). RGAP dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of $26.2{\pm}2.0$ ${\mu}g/ml$. In collagen-induced platelet aggregation, RGAP inhibited the reaction with an $IC_{50}$ value of $31.5{\pm}3.0\;{\mu}g/ml$. RGAP potently suppressed the intracellular calcium ion, which was stimulated by thrombin (0.1 U/ ml). Among mitogen-activated protein kinase (MAPK) subtypes, the extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK were analyzed in the present study. RGAP inhibited the phosphorylation of ERK2 and p38 MAPK, which was activated by collagen (2.5 ${\mu}g/ml$). Finally, these results suggested that besides saponin fraction, RGAP take an important role in the preventive effect of Korean red ginseng against cardiovascular disease such as thrombosis and atherosclerosis.