• Title/Summary/Keyword: signal molecules

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Signaling Mechanisms on the Vascular Relaxation of HMC05 (HMC05의 혈관이완 활성과 신호전달 작용기전)

  • Moon, Kug-Jin;Jang, Hyo-Oil;Kim, Gil-When;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.2
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    • pp.315-320
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    • 2008
  • This study investigated the signaling mechanisms contributed to the vasodilatory effects of HMC05, a herbal prescription. HMC05 acted in an endothelium-independent manner. To elucidate the fundamental mechanisms of its vascular actions, we focused on the signaling molecules involved in actin-myosin filament regulation including 20 kDa myosin light chains (LC20), Rho-associated kinase (ROCK), PKC, JNK and extracellular signal-regulated protein kinase (ERK) in the endothelium-denuded thoracic aorta or isolated smooth muscle cells (SMCs). It lowered the phosphorylation level of LC20 and showed that ROCK, ERK, JNK and $PKC{\alpha}$ pathways played important roles in the effects, as confirmed by the observations with a specific inhibition or activation, and with the activity and the subcellular localization of these molecules. In particular, HMC05 dramatically inhibited the activity of ERK and the downstream signaling of ROCK. It also changed the subcellular localization of the phophorylated $PKC{\alpha}$ as well as the amount of phosphorylation. Taken together, these data indicate that the vascular relaxation effects of HMC05 are attributed to the regulation of these signaling mechanisms.

Regulation by Reversible S-Glutathionylation: Molecular Targets Implicated in Inflammatory Diseases

  • Shelton, Melissa D.;Mieyal, John J.
    • Molecules and Cells
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    • v.25 no.3
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    • pp.332-346
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    • 2008
  • S-glutathionylation is a reversible post-translational modification that continues to gain eminence as a redox regulatory mechanism of protein activity and associated cellular functions. Many diverse cellular proteins such as transcription factors, adhesion molecules, enzymes, and cytokines are reported to undergo glutathionylation, although the functional impact has been less well characterized. De-glutathionylation is catalyzed specifically and efficiently by glutaredoxin (GRx, aka thioltransferase), and facile reversibility is critical in determining the physiological relevance of glutathionylation as a means of protein regulation. Thus, studies with cohesive themes addressing both the glutathionylation of proteins and the corresponding impact of GRx are especially useful in advancing understanding. Reactive oxygen species (ROS) and redox regulation are well accepted as playing a role in inflammatory processes, such as leukostasis and the destruction of foreign particles by macrophages. We discuss in this review the current implications of GRx and/or glutathionylation in the inflammatory response and in diseases associated with chronic inflammation, namely diabetes, atherosclerosis, inflammatory lung disease, cancer, and Alzheimer's disease, and in viral infections.

The protective effect of Prunella vulgaris ethanol extract against vascular inflammation in TNF-α-stimulated human aortic smooth muscle cells

  • Park, Sun Haeng;Koo, Hyun Jung;Sung, Yoon Young;Kim, Ho Kyoung
    • BMB Reports
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    • v.46 no.7
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    • pp.352-357
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    • 2013
  • Atherosclerosis, which manifests as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic inflammatory disease of the arterial wall. Prunella vulgaris, a perennial herb with a worldwide distribution, has been used as a traditional medicine in inflammatory disease. Here, we investigated the effects of P. vulgaris ethanol extract on TNF-${\alpha}$-induced inflammatory responses in human aortic smooth muscle cells (HASMCs). We found that P. vulgaris ethanol extract inhibited adhesion of monocyte/macrophage-like THP-1 cells to activated HASMCs. It also decreased expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and ROS, No production in TNF-${\alpha}$-induced HASMCs and reduced NF-${\kappa}B$ activation. Furthermore, P. vulgaris extract suppressed TNF-${\alpha}$-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). These results demonstrate that P. vulgaris possesses anti-inflammatory properties and can regulate TNF-${\alpha}$-induced expression of adhesion molecules by inhibiting the p38 MAPK/ERK signaling pathway.

Channel Capacity Analysis of DNA-based Molecular Communication with Length Encoding Mechanism

  • Xie, Jialin;Liu, Qiang;Yang, Kun;Lin, Lin
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.15 no.8
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    • pp.2923-2943
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    • 2021
  • The double helix structure of DNA makes it diverse, stable and can store information with high density, and these characteristics are consistent with the requirements of molecular communication for transport carriers. In this paper, a specific structure of molecular communication system based on DNA length coding is proposed. Transmitter (Tx) adopts the multi-layer golden foil design to control the release of DNA molecules of different lengths accurately, and receiver (Rx) adopts an effective and sensitive design of nanopore, and the biological information can be converted to the electric signal at Rx. The effect of some key factors, e.g., the length of time slot, transmission distance, the number of releasing molecules, the priori probability, on channel capacity is demonstrated exhaustively. Moreover, we also compare the transmission capacity of DNA-based molecular communication (DNA-MC) system and concentration-based molecular communication (MC) system under the same parameter setting, and the peak value of capacity of DNA-MC system can achieve 0.08 bps, while the capacity of MC system remains 0.025 bps. The simulation results show that DNA-MC system has obvious advantages over MC system in saving molecular resources and improving transmission stability.

Astaxanthin Ameliorates Atopic Dermatitis by Inhibiting the Expression of Signal Molecule NF-kB and Inflammatory Genes in Mice

  • Donghwan, Kim;Yong-Suk, Kim;Ho Sueb, Song
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.304-309
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    • 2022
  • Background: This study was conducted to determine the anti-inflammatory effect of astaxanthin, on atopic dermatitis. Methods: Changes in mouse body weight, lymph node weight, and the degree of improvement in symptoms were measured to determine the inflammatory response. Real-time reverse transcription-polymerase chain reaction tests were performed to determine the degree of expression of inflammation-related cytokines (IL-31 and IL-33 and chemokines such as CCL17 and CCL22), and western blot analysis was performed to evaluate the expression of inflammation-related factors (iNOS, COX-2, and NF-kB signaling molecules p-IkBα, p50, p-65 and pSTAT3). Results: The degree of symptoms significantly improved in the PA+AX group. Lymph node weight in the PA+AX group was lower than the PA group. Inflammatory cytokines (IL-31, IL-33, and inflammatory chemokines such as CCL17 and CCL22) were significantly reduced in the PA+AX group compared with the PA group. The expression of inflammatory genes (iNOS, COX-2, NF-kB and signaling molecules (p-IkBα, p50, p65, and p-STAT 3) was lower in the PA+AX group compared with the PA group. Conclusion: Astaxanthin may modulate the inflammatory response in a mouse model of atopic dermatitis and has an anti-inflammatory effect.

Inhibition of collagen-induced platelet aggregation by Sanggenon N via the Ca2+ signaling pathway

  • Hyuk-Woo Kwon
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.463-469
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    • 2022
  • Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A2 generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca2+ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser1756), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A2 generation and associated signaling molecules, including cytosolic phospholipase A2 and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β3) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

New Protein Extraction/Solubilization Protocol for Gel-based Proteomics of Rat (Female) Whole Brain and Brain Regions

  • Hirano, Misato;Rakwal, Randeep;Shibato, Junko;Agrawal, Ganesh Kumar;Jwa, Nam-Soo;Iwahashi, Hitoshi;Masuo, Yoshinori
    • Molecules and Cells
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    • v.22 no.1
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    • pp.119-125
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    • 2006
  • The rat is an accepted model for studying human psychiatric/neurological disorders. We provide a protocol for total soluble protein extraction using trichloroacetic acid/acetone (TCA/A) from rat (female) whole brain, 10 brain regions and the pituitary gland, and show that two-dimensional gel electrophoresis (2-DGE) using precast immobilized pH (4-7) gradient (IPG) strip gels (13 cm) in the first dimension yields clean silver nitrate stained protein profiles. Though TCA/A precipitation may not be "ideal", the important choice here is the selection of an appropriate lysis buffer (LB) for solubilizing precipitated proteins. Our results reveal enrichment of protein spots by use of individual brain regions rather than whole brain, as well as the presence of differentially expressed spots in their proteomes. Thus individual brain regions provide improved protein coverage and are better suited for differential protein detection. Moreover, using a phosphoprotein-specific dye, ingel detection of phosphoproteins was demonstrated. Representative high-resolution silver nitrate stained proteome profiles of rat whole brain total soluble protein are presented. Shortcomings apart (failure to separate membrane proteins), gel-based proteomics remains a viable option, and 2-DGE is the method of choice for generating high-resolution proteome maps of rat brain and brain regions.

Cytotoxicity of Anti-CD4 Antibody Activated $CD4^+$ T-Lymphocytes against Herpesvirus-Infected Target Cells is Dependent on $p56^{lck}$ and $p59^{fyn}$ Protein Tyrosine Kinase Activity

  • Choi, Sang-Hoon;Jang, Yong-Suk;Oh, Chan-Ho
    • BMB Reports
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    • v.31 no.4
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    • pp.355-363
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    • 1998
  • MHC unrestricted, antigen nonspecific killing by $CD4^+$ T-cells against virally-infected target cells was induced following cross-linking of CD4 molecules. The cytotoxicity of antibody-activated $CD4^+$ T-cells was abolished by genistein (4',5,7-trihydroxyisoflavone), a protein tyrosine kinase (PTK) inhibitor, but not by H-7, a protein kinase C (PKC) inhibitor. Genisteintreated human or bovine peripheral blood $CD4^+$ T-cells lacked PTK activity and failed to kill virally-infected target cells even after cross-linking of CD4 molecules. The cross-linking of CD4 molecules did not induce effector cell proliferation or the transcription of TNF ${\beta}$. TNF ${\beta}$ synthesis was up-regulated by incubating antibody activated effector cells with bovine herpesvirus type 1 (BHV-1) infected D17 target cells. Anti-TNF ${\beta}$ antibody partially abrogated direct effector cell-mediated antiviral cytotoxicity. On the other hand, this antibody effectively neutralized antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on effector and target cell ratio. These findings have importance to define the mechanisms of how CD4 cytotoxic cells control viral infection.

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Study on Electrochemical Detection of Cyclodextrin-molecule Interactions for Sensor Applications (센서 응용을 위한 사이클로덱스트린-분자 상호작용의 전기화학적 검출)

  • Park, Minji;Kim, Sooyeoun;Bae, Joonwon
    • Applied Chemistry for Engineering
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    • v.29 no.5
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    • pp.519-523
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    • 2018
  • Cyclodextrins are a class of oligosaccharides having an extremely low toxicity, so that they have been used for the formation of host-guest complexes and removal of toxic gases or molecules. In this study, the subtle phenomenon associated with the formation of host-guest complexes between cyclodextrin and toxic molecules (methyl paraben) was experimentally investigated. First, the formation of cyclodextrin-methyl paraben complexes was monitored by UV/Vis spectroscopy as a function of the cyclodextrin concentration. Secondly, the electrochemical measurement was performed with the surface engineered Au electrode having cyclodextrin molecules on the Au substrate. The sensing signal derived from the addition of methyl paraben solution into the Au surface was measured delicately. This study can be informative for future applications such as sensors.

Cross-linking of CD80 and CD86 Diminishes Expression of CD54 on EBV-transformed B Cells through Inactivation of RhoA and Ras

  • Park, Ga-Bin;Kim, Yeong-Seok;Song, Hyun-Keun;Kim, Seong-Han;Park, Dong-Man;Lee, Wang-Jae;Hur, Dae-Young
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.390-398
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    • 2011
  • Background: Epstein Barr virus (EBV) infected B cells are transformed into lymphoblastoid cell lines. Some researchers suggested some a few similarities between this process and carcinogenesis. We observed the expression of CD80 and CD86, co-stimulatory molecules on EBV-transformed B cells and changes of CD54 expression after stimulation of CD80 and CD86. Methods: CD80 and CD86 were stimulated using anti-CD80 and anti-CD86 monoclonal antibodies. To assess apoptosis and surface protein expression, flow cytometric analysis was performed. Intracellular signal molecules were evaluated by RT-PCR and immunoblot. Morphology and localization of proteins were examined using inverted or confocal microscope. Results: Cross-linking of CD80 and CD86 induced apoptosis and interfered with proliferation of EBV-transformed B cells, and dispersion of clumped cells. We also examined that their stimulation induced ROS accumulation and reduced CD54 expression. Interestingly, we observed that CD80 and CD86 diminished the expression of CD54 in different methods. Both CD80 and CD86 downregulated activation of focal adhesion kinase. CD80 stimulus inhibited CD54 expression through mainly RhoA inactivation, while CD86 down-regulated Ras and JNK phosphorylation. Conclusion: These results suggest that co-stimulatory CD80 and CD86 molecules, expressed EBV-transformed B cells, may play a role in apoptosis and cell adhesion.