• Title/Summary/Keyword: Blocking signal

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Inhibition of DNA-dependent Protein Kinase by Blocking Interaction between Ku Complex and Catalytic Subunit of DNA-dependent Protein Kinase

  • Kim, Chung-Hui;Cuong, Dang-Van;Kim, Jong-Su;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.1
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    • pp.9-14
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    • 2003
  • Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

Antimelanogenesis and skin-protective activities of Panax ginseng calyx ethanol extract

  • Lee, Jeong-Oog;Kim, Eunji;Kim, Ji Hye;Hong, Yo Han;Kim, Han Gyung;Jeong, Deok;Kim, Juewon;Kim, Su Hwan;Park, Chanwoong;Seo, Dae Bang;Son, Young-Jin;Han, Sang Yun;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.389-399
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    • 2018
  • Background: The antioxidant effects of Panax ginseng have been reported in several articles; however, little is known about the antimelanogenesis effect, skin-protective effect, and cellular mechanism of Panax ginseng, especially of P. ginseng calyx. To understand how an ethanol extract of P. ginseng berry calyx (Pg-C-EE) exerts skin-protective effects, we studied its activities in activated melanocytes and reactive oxygen species (ROS)-induced keratinocytes. Methods: To confirm the antimelanogenesis effect of Pg-C-EE, we analyzed melanin synthesis and secretion and messenger RNA and protein expression levels of related genes. Ultraviolet B (UVB) and hydrogen peroxide ($H_2O_2$) were used to induce cell damage by ROS generation. To examine whether this damage is inhibited by Pg-C-EE, we performed cell viability assays and gene expression and transcriptional activation analyses. Results: Pg-C-EE inhibited melanin synthesis and secretion by blocking activator protein 1 regulatory enzymes such as p38, extracellular signal-regulated kinases (ERKs), and cyclic adenosine mono-phosphate response element-binding protein. Pg-C-EE also suppressed ROS generation induced by $H_2O_2$ and UVB. Treatment with Pg-C-EE decreased the expression of matrix metalloproteinases, mitogen-activated protein kinases, and hyaluronidases and increased the cell survival rate. Conclusion: These results suggest that Pg-C-EE may have antimelanogenesis properties and skin-protective properties through regulation of activator protein 1 and cyclic adenosine monophosphate response element-binding protein signaling. Pg-C-EE may be used as a skin-improving agent, with moisture retention and whitening effects.

A Study on Call Admission Control Scheme based on Multiple Thresholds in the CDMA System (CDMA시스템에서 다중 종류의 문턱치를 사용한 호 수락제어 기법에 대한 연구)

  • Piao, Shi-Gwon;Park, Yong-Wan
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.28 no.3A
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    • pp.129-139
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    • 2003
  • CAC is a very important issue in CDMA system in order to protect the required QoS(quality of service) and increase the system's capacity. In this paper, we proposed and analyzed a call admission control scheme using multiple thresholds, which can provide quick processing time and better performance. There are two effective thresholds used to decide call admission. One is the number of active users, and the other is the signal to interference ratio(SIR). If the threshold of active users are lower than the low number of users threshold, we accept the new call without any other conditions. Otherwise, we check the current SIR to guarantee the quality of our service. System then accepts the new call when the SIR satisfies system requirement. Otherwise, the call will be rejected. Multiple threshold schemes are investigated and their performance is compared with the number of user and power based CAC's. simulation results are provided to evaluate the performance.

Recombinant human KAI1/CD82 attenuates M1 macrophage polarization on LPS-stimulated RAW264.7 cells via blocking TLR4/JNK/NF-κB signal pathway

  • Hyesook Lee;Jung-Hwa Han;Kangbin An;Yun Jeong Kang;Hyun Hwangbo;Ji Hye Heo;Byung Hyun Choi;Jae-Joon Kim;Seo Rin Kim;Soo Yong Lee;Jin Hur
    • BMB Reports
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    • v.56 no.6
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    • pp.359-364
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    • 2023
  • KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

THE EFFECT OF BMP REGULATED SMAD PROTEIN ON ALKALINE PHOSPHATASE GENE EXPRESSION (Smad에 의한 alkaline phosphatase 유전자의 발현 조절기전)

  • Kim, Nan-Jin;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.2
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    • pp.238-246
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    • 2001
  • Bone morphogenetic proteins(BMPs), members of the transforming growth factor $\beta$(TGF-$\beta$) superfamily were first identified as the factors that induce ectopic bone formation in vivo, when implanted into muscular tissue. Especially BMP-2 inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells. In the molecular mechanism of the signal transduction of TGF-$\beta$ and related factors, intracellular signaling proteins were identified as Smad. In previous study, it has been reported that Smad 1 and Smad 5, which belong to the R-Smad family mediate BMP signaling, were involved in the induction of osteoblast differentiation in C2C12 cells. To understnad the role of Smads involved in osteogenic transdifferentiation in C2C12 cell, in present study, after we stably transfected C2C12 cells with each. Smad(Smad 1,Smad 5) expression vector, cultured for 3 days and stained for alkaline phophatase activity. ALP activity positive cells appeared in the Smad 1, Smad 5 stably transfected cell even in the abscence of BMP. After transiently co-transfected C2C12 cells with each Smad expression vector and ALP promoter, it was examined that Smad 1 and Smad 5 expression vector had increased about 2 fold ALP promoter activity in the abscence of BMP. These result suggested that both Smad 1 and Smad 5 were involved in the intracellular BMP signals which induce osteoblast differentiation in C2C12 cells. The effect of BMP on C2C12 cells with Smad 1, Smad 5 transfected were studied by using northern blot analysis. the treatment of BMP upregulated ALP mRNA level in three groups, especially upregulation of ALP was larger in Smad 1, Smad 5 transfected cell than control group. Pretreatment with cycloheximide($10{\mu}g/ml$), a protein synthesis inhibitor resulted in blocking the ALP gene expression even in BMP(100ng/ml) treated cell. These results suggested that Smad increased the level of ALP mRNA via the synthesis of a certain transcriptional regulatory protein.

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Inhibitory Effect of Protaetiamycine 9 Derived from Protaetia brevitarsis seulensis Larvae on LPS-mediated Inflammation in RAW264.7 Cells (LPS로 자극한 RAW264.7 대식세포에서 흰점박이꽃무지 유충 유래 Protaetiamycine 9의 항염증 효과)

  • Choi, Ra-Yeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.31 no.11
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    • pp.987-994
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    • 2021
  • Our previous studies have reported that antimicrobial peptides (AMPs) derived from the larvae of white-spotted flower chafer (Protaetia brevitarsis seulensis) exert anti-inflammatory and neuroprotective activities. This study explored the anti-inflammatory effects of protaetiamycine 9 (CVLKKAYFLTNLKLRG-NH2), a novel AMP, derived from P. b. seulensis against lipopolysaccharide (LPS)-mediated inflammatory response in RAW264.7 macrophage cells. Protaetiamycine 9 (25, 50, 75, and 100 ㎍/ml) did not cause cytotoxic effects against RAW264.7 cells. The RAW264.7 cells were pre-treated with various concentrations of protaetiamycine 9 (25-100 ㎍/ml) for 1 hr and then exposed to LPS (100 ng/ml) for 24 hr. Protaetiamycine 9 treatments decreased the LPS-induced secretion of inflammatory mediators, such as nitric oxide (NO), in a dose-dependent manner. Protaetiamycine 9 (25-100 ㎍/ml) effectively downregulated the LPS-induced increase in mRNA and the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. Protaetiamycine 9 also suppressed the production and gene expression of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, compared to the presence of LPS alone. Furthermore, protaetiamycine 9 inhibited the degradation of inhibitory kappa B alpha (IκB-α) and the phosphorylation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In conclusion, these results suggest that protaetiamycine 9 exhibits LPS-mediated inflammatory responses by blocking IκB-α degradation and MAPK phosphorylation.

Image Watermarking for Copyright Protection of Images on Shopping Mall (쇼핑몰 이미지 저작권보호를 위한 영상 워터마킹)

  • Bae, Kyoung-Yul
    • Journal of Intelligence and Information Systems
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    • v.19 no.4
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    • pp.147-157
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    • 2013
  • With the advent of the digital environment that can be accessed anytime, anywhere with the introduction of high-speed network, the free distribution and use of digital content were made possible. Ironically this environment is raising a variety of copyright infringement, and product images used in the online shopping mall are pirated frequently. There are many controversial issues whether shopping mall images are creative works or not. According to Supreme Court's decision in 2001, to ad pictures taken with ham products is simply a clone of the appearance of objects to deliver nothing but the decision was not only creative expression. But for the photographer's losses recognized in the advertising photo shoot takes the typical cost was estimated damages. According to Seoul District Court precedents in 2003, if there are the photographer's personality and creativity in the selection of the subject, the composition of the set, the direction and amount of light control, set the angle of the camera, shutter speed, shutter chance, other shooting methods for capturing, developing and printing process, the works should be protected by copyright law by the Court's sentence. In order to receive copyright protection of the shopping mall images by the law, it is simply not to convey the status of the product, the photographer's personality and creativity can be recognized that it requires effort. Accordingly, the cost of making the mall image increases, and the necessity for copyright protection becomes higher. The product images of the online shopping mall have a very unique configuration unlike the general pictures such as portraits and landscape photos and, therefore, the general image watermarking technique can not satisfy the requirements of the image watermarking. Because background of product images commonly used in shopping malls is white or black, or gray scale (gradient) color, it is difficult to utilize the space to embed a watermark and the area is very sensitive even a slight change. In this paper, the characteristics of images used in shopping malls are analyzed and a watermarking technology which is suitable to the shopping mall images is proposed. The proposed image watermarking technology divide a product image into smaller blocks, and the corresponding blocks are transformed by DCT (Discrete Cosine Transform), and then the watermark information was inserted into images using quantization of DCT coefficients. Because uniform treatment of the DCT coefficients for quantization cause visual blocking artifacts, the proposed algorithm used weighted mask which quantizes finely the coefficients located block boundaries and coarsely the coefficients located center area of the block. This mask improves subjective visual quality as well as the objective quality of the images. In addition, in order to improve the safety of the algorithm, the blocks which is embedded the watermark are randomly selected and the turbo code is used to reduce the BER when extracting the watermark. The PSNR(Peak Signal to Noise Ratio) of the shopping mall image watermarked by the proposed algorithm is 40.7~48.5[dB] and BER(Bit Error Rate) after JPEG with QF = 70 is 0. This means the watermarked image is high quality and the algorithm is robust to JPEG compression that is used generally at the online shopping malls. Also, for 40% change in size and 40 degrees of rotation, the BER is 0. In general, the shopping malls are used compressed images with QF which is higher than 90. Because the pirated image is used to replicate from original image, the proposed algorithm can identify the copyright infringement in the most cases. As shown the experimental results, the proposed algorithm is suitable to the shopping mall images with simple background. However, the future study should be carried out to enhance the robustness of the proposed algorithm because the robustness loss is occurred after mask process.

Auranofin Downregulates Nuclear Factor-κB Activation via Nrf2-Independent Mechanism (오라노핀에 의한 nuclear factor κB 활성저해는 Nrf2 활성화와 무관한 기전에 의함)

  • Kim, Nam-Hoon;Park, Hyo-Jung;Kim, In-Sook
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1772-1776
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    • 2010
  • Transcription factors Nrf2 and NF-${\kappa}B$ are important regulators of the innate immune response, and their cross-talks in inflammation have been reported. Previously, we demonstrated that gold(I)-compound auranofin, an inhibitor of NF-${\kappa}B$ signal, induced Nrf2 activation in human synovial cells and monocytic cells. To investigate whether the Nrf2 activation is involved in the mechanism of the auranofin-attenuated NF-${\kappa}B$ signaling, we examined the effects of Nrf2 knockdown on NF-${\kappa}B$ activation using rheumatic synovial cells. When the cells were transfected with a specific siRNA for Nrf2, the gene expression was perfectly blocked. However, the Nrf2 knockdown did not cancel the suppressive effect of auranofin on TNF-$\alpha$-induced $I{\kappa}B-{\alpha}$ degradation. Treatment with a specific siRNA for HO-1, which is a target of Nrf2 and plays a role in anti-inflammation, also did not affect the blocking activity of auranofin on $I{\kappa}B-{\alpha}$ degradation. In addition, auranofin-inhibited ICAM-1 expression was not restored by Nrf2 knockdown. These findings indicate that the activated Nrf2 and HO-1 are not associated with the suppressive action of auranofin on the pro-inflammatory cytokines-stimulated NF-${\kappa}B$ activation. This suggests that Nrf2/HO-1 and NF-${\kappa}B$ signals, which are regulated by auranofin, participate in the anti-inflammatory action of auranofin via independent pathways in rheumatic synovial cells.

Operation Measures of Sea Fog Observation Network for Inshore Route Marine Traffic Safety (연안항로 해상교통안전을 위한 해무관측망 운영방안에 관한 연구)

  • Joo-Young Lee;Kuk-Jin Kim;Yeong-Tae Son
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.29 no.2
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    • pp.188-196
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    • 2023
  • Among marine accidents caused by bad weather, visibility restrictions caused by sea fog occurrence cause accidents such as ship strand and ship bottom damage, and at the same time involve casualties caused by accidents, which continue to occur every year. In addition, low visibility at sea is emerging as a social problem such as causing considerable inconvenience to islanders in using transportation as passenger ships are collectively delayed and controlled even if there are local differences between regions. Moreover, such measures are becoming more problematic as they cannot objectively quantify them due to regional deviations or different criteria for judging observations from person to person. Currently, the VTS of each port controls the operation of the ship if the visibility distance is less than 1km, and in this case, there is a limit to the evaluation of objective data collection to the extent that the visibility of sea fog depends on the visibility meter or visual observation. The government is building a marine weather signal sign and sea fog observation networks for sea fog detection and prediction as part of solving these obstacles to marine traffic safety, but the system for observing locally occurring sea fog is in a very insufficient practical situation. Accordingly, this paper examines domestic and foreign policy trends to solve social problems caused by low visibility at sea and provides basic data on the need for government support to ensure maritime traffic safety due to sea fog by factually investigating and analyzing social problems. Also, this aims to establish a more stable maritime traffic operation system by blocking marine safety risks that may ultimately arise from sea fog in advance.