• Title/Summary/Keyword: signal pathway

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Suppression of Prostaglandin E2-Mediated Cell Proliferation and Signal Transduction by Resveratrol in Human Colon Cancer Cells

  • Song, Su-Hyun;Min, Hye-Young;Lee, Sang-Kook
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.402-410
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    • 2010
  • Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

Understanding of Drought Stress Signaling Network in Plants (식물의 물부족 스트레스 신호 전달 네트워크에 대한 이해)

  • Lee, Jae-Hoon
    • Journal of Life Science
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    • v.28 no.3
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    • pp.376-387
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    • 2018
  • Among a variety of environmental stresses heat, cold, chilling, high salt, drought, and so on exposed to plants, drought stress has been reported as a crucial factor to adversely affect the growth and productivity of plants. Therefore, to understand the mechanism for the drought stress signal transduction pathway in plants is more helpful to develop useful crops that display the enhanced tolerance against drought stress, and to expand crop growing areas. The signal transduction pathway for the drought stress in plants is largely categorized into two types; ABA-dependent pathway and ABA-independent pathway. It has been reported that two transcription factors, AREB/ABF and DREB2, play predominant roles in ABA-dependent and ABA-independent pathways, respectively. In addition to transcriptional regulation mediated by AREB/ABF and DREB2 transcription factors, post-translational modification (such as phosphorylation and ubiquitination) and epigenetic control are importantly involved in the signal transduction for drought stress. In this paper, we review current understanding of signal transduction pathway on drought stress in plants, especially focusing on the biological roles of a variety of signaling components related to drought stress response. Further understanding the mechanism of drought resistance in plants through this review will be useful to establish theoretical basis for developing drought tolerant crops in the future.

The cAMP/Protein Kinase A Pathway and Virulence in Cryptococcus neoformans

  • Kronstad, James W.;Hu, Guang-Gan;Choi, Jae-Hyuk
    • Mycobiology
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    • v.39 no.3
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    • pp.143-150
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    • 2011
  • The basidiomycete fungus Cryptococcus neoformans is an important pathogen of immunocompromised people. The ability of the fungus to sense its environment is critical for proliferation and the generation of infectious propagules, as well as for adaptation to the mammalian host during infection. The conserved cAMP/protein kinase A pathway makes an important contribution to sensing, as demonstrated by the phenotypes of mutants with pathway defects. These phenotypes include loss of the ability to mate and to elaborate the key virulence factors capsule and melanin. This review summarizes recent work that reveals new targets of the pathway, new phenotypic consequences of signaling defects, and a more detailed understanding of connections with other aspects of cryptococcal biology including iron regulation, pH sensing, and stress.

pH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals

  • Selvig, Kyla;Alspaugh, J. Andrew
    • Mycobiology
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    • v.39 no.4
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    • pp.249-256
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    • 2011
  • Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast-like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host.

Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development

  • Ha, Woo Tae;Jeong, Ha Yeon;Lee, Seung Yoon;Song, Hyuk
    • Development and Reproduction
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    • v.20 no.3
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    • pp.179-185
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    • 2016
  • The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

A Metabolic Pathway Drawing Algorithm for Reducing the Number of Edge Crossings

  • Song Eun-Ha;Kim Min-Kyung;Lee Sang-Ho
    • Genomics & Informatics
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    • v.4 no.3
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    • pp.118-124
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    • 2006
  • For the direct understanding of flow, pathway data are usually represented as directed graphs in biological journals and texts. Databases of metabolic pathways or signal transduction pathways inevitably contain these kinds of graphs to show the flow. KEGG, one of the representative pathway databases, uses the manually drawn figure which can not be easily maintained. Graph layout algorithms are applied for visualizing metabolic pathways in some databases, such as EcoCyc. Although these can express any changes of data in the real time, it exponentially increases the edge crossings according to the increase of nodes. For the understanding of genome scale flow of metabolism, it is very important to reduce the unnecessary edge crossings which exist in the automatic graph layout. We propose a metabolic pathway drawing algorithm for reducing the number of edge crossings by considering the fact that metabolic pathway graph is scale-free network. The experimental results show that the number of edge crossings is reduced about $37{\sim}40%$ by the consideration of scale-free network in contrast with non-considering scale-free network. And also we found that the increase of nodes do not always mean that there is an increase of edge crossings.

Immune enhancing activity of Sargassum horneri extracts via MAPK pathway in macrophages (대식세포에서 괭생이모자반 추출물의 MAPKs 기전 통한 면역활성 증가 효과)

  • 김동섭;김민지;성낙윤;한인준;김건;김춘성;유영춘;정윤우
    • Journal of Marine Bioscience and Biotechnology
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    • v.15 no.1
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    • pp.12-23
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    • 2023
  • Sargassum horneri (SH), a brown macroalgae, has medicinal properties. The present study investigated the immune-enhancing effects of SH extract on peritoneal macrophages (PM). The SH significantly increased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in PM. It was confirmed that SH significantly increased NO expression through the increase of iNOS protein expression, which is the up-regulation pathway. Additionally, it was determined if SH activates the mitogen-activated protein kinase (MAPK) pathway, an upper regulatory mechanism that influences TNF-α, IL-6, and NO expression. Consequently, SH significantly increased the phosphorylation of p38, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK), all of which are MAPK pathway proteins. Moreover, the immune-enhancing effects of SH on another macrophage cell line, bone marrow-derived macrophages were investigated. It was observed that SH significantly enhanced TNF-α, IL-6, and NO production. Overall, this study demonstrates the immune-enhancing effects of SH on macrophages via activated MAPK pathway. Therefore, it suggests that SH has the potential to improve immunological activity in various macrophage cell lines and can be useful as an immune-enhancing treatment.

Regulation of Interleukin-17 Production in Patients with Rheumatoid Arthritis by Phosphoinositide 3-kinase (PI3K)/Akt and Nuclear Factor KappaB (NF-κB) Dependent Signal Transduction Pathway (류마티스 관절염 환자의 말초혈액 단핵세포에서 Phosphoinositide 3-Kinase (PI3K)/Akt와 Nuclear Factor KappaB (NF-κB) 신호전달을 통한 IL-17 생성조절)

  • Kim, Kyoung-Woon;Cho, Mi-La;Lee, Sang-Heon;Min, So-Youn;Park, Mi Kyung;Park, Sung-Hwan;Jue, Dae-Myung;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.4
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    • pp.310-319
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    • 2003
  • Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

Effect of Simetryne on Chloroplast-Mediated Electron Transport and Photoacoustic Signal (엽록체의 전자전달과 광음향 신호에 미치는 Simetryne의 영향)

  • 김현식
    • Journal of Plant Biology
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    • v.31 no.3
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    • pp.205-215
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    • 1988
  • The effects of simetryne on light induced electron transport and phosphorylation in isolated spinach (Spinacia oleracea L.) chloroplasts were investigated in comparison with sencor and DCMU. Simetryne, like sencor and DCMU, completely, inhibited PSII electron transport and phosphoryltion with 10-6 M treatment but did not inhibit PSI electron transport. Interference with the electron transport pathway was evidenced by the greater sensitivity of oxygen evolution and uptake than phosphorylation. The following order of decreasing inhibitory effectiveness was exihibited; DCMU>simetryne>sencor. The photoacoustic technique was also used to monitor the relative photosynthetic activity in the leaves treated with the herbicides (simetryne, sencor or DCMU) in vivo and in vitro. Photoacoustic measurements on intact leaves provide quantitative information on two related aspects of the photosynthetic process, namely, photochemical energy storage and oxygen evolution. The relative photoacoustic signal of leaves treated with the herbicides showed low level in 21 Hz, but high level in 380 Hz and on isolated chloroplasts (both 21 Hz and 380 Hz) in comparison with that of the untreated leaves. These results suggest that some of photochemical energy is converted into the heat owing to the inhibition of electorn transport pathway by the herbicides.

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