• Title/Summary/Keyword: S100A4

Search Result 7,555, Processing Time 0.041 seconds

S100A4 Expression is Closely Linked to Genesis and Progression of Glioma by Regulating Proliferation, Apoptosis, Migration and Invasion

  • Jin, Ting;Zhang, Zhuo;Yang, Xue-Feng;Luo, Jun-Sheng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.7
    • /
    • pp.2883-2887
    • /
    • 2015
  • Background: The calcium-binding S100A4 protein is involved in epithelial to mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity, mobility and metastasis of cancer cells. This study aimed to clarify the roles of S100A4 in genesis and progression of glioma. Materials and Methods: S100A4 expression was examined by real-time RT-CPR and Western blot in glioma and paired normal brain tissue (n=69), and compared with clinicopathological parameters of tumors. In addition, glioma U251 cells transfected with an S100A4-expressing plasmid were examined for proliferation by MTT, apoptosis by Annexin V-FITC, and migration and invasion with Transwell chambers. Results: Increased S100A4 mRNA expression was found in gliomas, compared with paired non-tumor tissue (p<0.001). Gradual elevation of overexpression of S100A4 was observed with increasing glioma grade (p<0.001). Astrocytoma showed lower S100A4 mRNA expression than oligodendrogliomas, with glioblastomas having highest values (p<0.001). Similar results were obtained for S100A4 protein, a positive link being found between mRNA and protein expression in gliomas (p<0.001). There was higher growth, lower apoptosis, stronger migration and invasion of S100A4 transfectants than control and mock transfected cells (p<0.001). Conclusions: These findings indicate that up-regulated S100A4 expression is positively linked to pathogenesis, progression and histogenesis of glioma by modulating proliferation, apoptosis, migration and invasion.

The Pro-apoptotic Effects of S100A8 and S100A9 in Human Monocytic Leukemia Cells, THP-1

  • Kim, In-Sik;Lee, Ji-Sook
    • Biomedical Science Letters
    • /
    • v.24 no.2
    • /
    • pp.134-137
    • /
    • 2018
  • S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

Expression of Periostin and S100A2 - S100A4 - Calcium Binding Proteins mRNA in Human Gingival Fibroblasts and Periodontal Ligament Fibroblasts (사람 치은섬유세포와 치주인대섬유모세포에서 Periostin과 S100A2-, S100A4-칼슘결합단백 mRNA의 발현)

  • Kim, Byung-Ock;Han, Kyung-Yoon;Choi, Young-Sun;Kim, Se-Hoon;Park, Byung-Gi;Kim, Heung-Joong;Park, Joo-Cheol
    • Journal of Periodontal and Implant Science
    • /
    • v.31 no.1
    • /
    • pp.109-122
    • /
    • 2001
  • Gingival fibroblasts(GF) and periodontal ligament fibroblasts(PDLF) are the major cellular components of periodontal soft connective tissues, but the precise molecular biological differences between these cells are not yet known. In the present study, we investigated the expression of S100A4, S100A2 calcium-binding protein and osteoblast-specific factor 2(OSF-2, Periostin) mRNA in GF and PDLF in vitro through the process of reverse transcription-polymerase chain reaction(RT-PCR) and Northern blot analysis in each. Human GF and PDLF were isolated from the gingival connective tissue and the middle third of freshly extracted healthy third molars. They were cultured in Dulbecco's Modified Eagle Medium(DMEM) containing 10% fetal bovine serum and cells in the third passage were used in the experiments. After extracting total RNA from cultured cells, RT-PCR and Northern analysis were performed using S100A4-, S100A2- and Periostin-specific oligonucleotide primers and subcloned cDNA probes in each. In PT-PCR and Northern analysis, the expression of S100A4 and Periostin mRNA in GF was slightly detectable. Interestingly, the expression of S100A4 and periostin mRNA in PDLF was much higher than that in GF. On the other hand, S100A2 mPNA was highly expressed in both GF and PDLF. Since there was a marked difference of S100A4 and Periostin expression between GF and PDLF in vitro, these data suggest that S100A4 and periostin could be used as a useful marker for distinguishing cultured gingival fibroblasts and periodontal ligament cells.

  • PDF

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

  • Zhang, Yin-Hua;Ma, De-Qiang;Ding, De-Ping;Li, Juan;Chen, Lin-Li;Ao, Kang-Jian;Tian, You-You
    • Yonsei Medical Journal
    • /
    • v.59 no.9
    • /
    • pp.1064-1071
    • /
    • 2018
  • Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

S100A8 Induces Secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T Cells

  • Nam, A Reum;Kim, Da Hae;Kim, Mun Jeong;Lee, Ji-Sook;Yang, Seung-Ju;Kim, In Sik
    • Biomedical Science Letters
    • /
    • v.22 no.2
    • /
    • pp.60-64
    • /
    • 2016
  • In the pathogenesis of inflammatory diseases such as allergies, S100A8 acts as an important molecule and T lymphocytes are essential cytokine-releasing cells. In this study, we investigated the effect of S100A8 on release of cytokines, specifically MCP-1, IL-6, and IL-8 in T cells, and its associated signaling mechanism. S100A8 increased secretion of MCP-1, IL-6, and IL-8 in a time- and dose-dependent manner. Elevated secretion of MCP-1, IL-6, and IL-8 due to S100A8 was inhibited by the TLR4 inhibitor TLR4i, the PI3K inhibitor LY294002, the $PKC{\delta}$ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF-${\kappa}B$ inhibitor BAY-11-7085. S100A8 induced phosphorylation of ERK, p38 MAPK, and JNK in a time-dependent manner, and activation was suppressed by TLR4i, LY294002, and rottlerin. S100A8 induced NF-${\kappa}B$ activation by $I{\kappa}-B{\alpha}$ degradation, and NF-${\kappa}B$ activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, $PKC{\delta}$, MAPKs, and NF-${\kappa}B$ will contribute to elucidation of the S100A8-invovled mechanism.

Extracellular S100A4 negatively regulates osteoblast function by activating the NF-κB pathway

  • Kim, Haemin;Lee, Yong Deok;Kim, Min Kyung;Kwon, Jun-Oh;Song, Min-Kyoung;Lee, Zang Hee;Kim, Hong-Hee
    • BMB Reports
    • /
    • v.50 no.2
    • /
    • pp.97-102
    • /
    • 2017
  • Patients with inflammatory bone disease or cancer exhibit an increased risk of fractures and delayed bone healing. The S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. We investigated the effects of extracellular S100A4 on osteoblasts, which are cells responsible for bone formation. Treating primary calvarial osteoblasts with recombinant S100A4 resulted in matrix mineralization reductions. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed. Interestingly, S100A4 stimulated the nuclear factor-kappaB (NF-${\kappa}B$) signaling pathway in osteoblasts. More importantly, the ex vivo organ culture of mouse calvariae with recombinant S100A4 decreased the expression levels of osteocalcin, supporting the results of our in vitro experiments. This suggests that extracellular S100A4 is important for the regulation of bone formation by activating the NF-${\kappa}B$ signaling pathway in osteoblasts.

Characterization of the Monoclonal Antibody Specific to Human S100A2 Protein (인체 S100A2 단백질에 특이적인 단일클론 항체)

  • Kim, Jae Wha;Yoon, Sun Young;Kim, Joo Heon;Joo, Jong-Hyuck;Kim, Jin Sook;Lee, Younghee;Yeom, Young Il;Choe, Yong-Kyung;Choe, In Seong
    • IMMUNE NETWORK
    • /
    • v.3 no.1
    • /
    • pp.16-22
    • /
    • 2003
  • Background: The S100A2 gene, also known as S100L or CaN19, encodes a protein comprised of 99-amino acids, is a member of the calcium-binding proteins of EF-hand family. According to a recent study, this gene was over-expressed in several early and malignant carcinomas compared to normal tissues. To elucidate the role of S100A2 protein in the process during carcinogenesis, production of monoclonal antibody specific to the protein is essential. Methods: First, cDNA sequence coding for ORF region of human S100A2 gene was amplified and cloned into an expression vector to produce GST fusion protein. Recombinant S100A2 protein and subsequently, monoclonal antibody to the protein were produced. The specificity of anti-S100A2 monoclonal antibody was confirmed by immunoblot analysis of cross reactivity to other recombinant proteins of S100A family (GST-S100A1, GST-S100A4 and GST-S100A6). To confirm the relation of S100A2 to cervical carcinogenesis, S100A2 protein in early cervical carcinoma tissue was immunostained using the monoclonal antibody. Results: GST-S100A2 recombinant protein was purified by affinity chromatography and then fusion protein was cleaved and S100A2 protein was isolated. The monoclonal antibody (KK0723; Korean patent pending #2001-30294) to the protein was produced and the antibody did not react with other members of EF-hand family proteins such as S100A1, S100A4 and S100A6. Conclusion: These data suggest that anti-S100A2 monoclonal antibody produced in this study can be very useful for the early detection of cervical carcinoma and elucidation of mechanism during the early cervical carcinogenesis.

A Study of Mg Capping Inside p-tert-butylcalix[4]arene Adsorbed on a Ge(100) Surface

  • Shin, Minjeong;Lee, Myungjin;Lee, Hangil
    • Proceedings of the Korean Vacuum Society Conference
    • /
    • 2013.08a
    • /
    • pp.135-135
    • /
    • 2013
  • The electronic and adsorption structures of Mg and p-tert-butylcalix[4]arene (p-TBCA) adsorbed onto a Ge(100) surface under a variety of sample conditions were characterized using high-resolution photoemission spectroscopy (HRPES) and their corresponding DFT calculation results. Interestingly, after 0.10 ML p-TBCA molecules had been adsorbed onto a Ge(100) surface, subsequent adsorption of a small amount of metallic Mg (~0.10 ML) resulted in the formation of a capped structure inside the pre-adsorbed p-TBCA molecules. The adsorption structures resulting from further deposition of Mg (~0.50 ML) onto the Ge(100) surface were monitored based on the surface charge state and Mg 2s core level spectrum. Work function measurements clearly indicated the electronic structures of the Mg and p-TBCA adsorbed onto the Ge(100) surface. Moreover, we confirmed that three different adsorption structures are experimentally favorable at room temperature through DFT calculation results.

  • PDF

Analysis of Pathogenic Microorganism's Contamination on Cultivation Environment of Strawberry and Tomato in Korea

  • Oh, Soh-Young;Nam, Ki-Woong;Kim, Won-Il;Lee, Mun Haeng;Yoon, Deok-Hoon
    • Korean Journal of Soil Science and Fertilizer
    • /
    • v.47 no.6
    • /
    • pp.510-517
    • /
    • 2014
  • The purpose of this study was to analyze microbial hazards for cultivation environments and personal hygiene of strawberry and tomato farms at the growth and harvesting stage. Samples were collected from thirty strawberry farms and forty tomato farms located in Korea and tested for Staphylococcus aureus and Bacillus cereus. To investigate the change in the distribution of the S. aureus and B. cereus, a total of 4,284 samples including air born, soil or medium, mulching film, harvest basket, groves and irrigation water etc. were collected from eight strawberry farms and nine tomato farms for one year. As a result, total S. aureus and B. cereus in all samples were detected. Among the total bacteria of strawberry farms, S. aureus (glove: $0{\sim}2.1Log\;CFU/100cm^2$, harvest basket: $0{\sim}3.0Log\;CFU/100cm^2$, soil or culture media: 0~4.1 Log CFU/g, mulching film: $0{\sim}3.8Log\;CFU/100cm^2$), B. cereus (glove: $0{\sim}2.8Log\;CFU/100cm^2$, harvest basket: $0{\sim}4.8Log\;CFU/100cm^2$, soil or culture media: 0~5.3 Log CFU/g, mulching film: $0{\sim}4.5Log\;CFU/100cm^2$) were detected in all samples. The total bacteria of tomato farms, S. aureus (glove: $0{\sim}4.0Log\;CFU/100cm^2$, harvest basket: $0{\sim}5.0Log\;CFU/100cm^2$, soil or culture media: 0~6.1 Log CFU/g, mulching film: $0{\sim}4.0Log\;CFU/100cm^2$), B. cereus (glove: $0{\sim}4.0Log\;CFU/100cm^2$, harvest basket: $0{\sim}4.3Log\;CFU/100cm^2$, soil or culture media: 0~5.9 Log CFU/g, mulching film: $0{\sim}4.7Log\;CFU/100cm^2$) were detected in all samples. The contamination of S. aureus and B. cereus were detected in soil, mulching film and harvest basket from planting until harvest to processing, with the highest count recorded from the soil. But S. aureus and B. cereus were not detected in irrigation water samples. The incidence of S. aureus and B. cereus in hydroponics culture farm were less than those in soil culture. The amount of S. aureus and B. cereus detected in strawberry and tomato farms were less than the minimum amount required to produce a toxin that induces food poisoning. In this way, the degree of contamination of food poisoning bacteria was lower in the production environment of the Korea strawberry and tomato, but problems can be caused by post-harvest management method. These results will be used as fundamental data to create a manual for sanitary agricultural environment management, and post-harvest management should be performed to reduce the contamination of hazardous microorganisms.

A Design of Data Model for Marine casualty based on S-100 (S-100 표준 기반 해양 사고 데이터 모델 설계)

  • Kim, Hyoseung;Mun, Changho;Lee, Seojeong
    • Journal of Digital Contents Society
    • /
    • v.18 no.4
    • /
    • pp.769-775
    • /
    • 2017
  • The International Maritime Organization's e-Navigation strategy is to introduce new technologies to ships to support easier and safer navigation. With the e-Navigation strategy, various equipment will be installed in vessels and the system structure will be linked to onshore systems. For this reason, a common data structure between systems became necessary, and finally the S-100 standard developed by the International Hydrographic Organization was selected. This paper describes a design of marine casualty data model based on the S-100 standard. The data model of the S-100 standard is designed in the form of a UML class diagram, and the final encoding follows the GML / XML format. We will look at the S-100 standard and product specifications under development, and describe the S-100 standards-based data design and portrayal definition of marine accident data.