• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.499-503
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• 2012

The present study was based on the unexpected discovery that norcantharidin exerted anti-angiogenesis activity when effects on growth of human colon cancer were studied. The aim was to further verify this finding and explore possible mechanisms using a tumor xenograft model in nude mice. We confirmed that norcantharidin (5 or 15 mg/kg) could inhibit angiogenesis of human colon cancer in vivo. In vitro, crossing river assay, cell adhesion assay and tube formation assay indicated that NCTD could reduce the migration, adhesion and vascular network tube formation ability of HUVECs. At the same time, the expression levels of VEGF and VEGFR-2 proteins which play important roles in angiogenesis were reduced as examined by western blotting analysis. Taken together, the results firstly showed NCTD could inhibit angiogenesis of human colon cancer in vivo, probably associated with effects on migration, adhesion and vascular network tube formation of HUVECs and expression levels of VEGF and VEGFR-2 proteins.

• Journal of Microbiology and Biotechnology
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• 제20권6호
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• pp.978-984
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• 2010

This paper examines the probiotic bacterium Lactobacillus rhamnosus GG, and how it reacts to the presence of mucin in its extracellular milieu. Parameters studied included cell clustering, adhesion to mucin, extracellular protein production, and formation of final metabolites. L. rhamnosus GG was found to grow efficiently in the presence of glucose, N-acetylglucosamine, or mucin (partially purified or purified) as sole carbon sources. However, it was unable to grow using other mucin constituents, such as fucose or glucuronic acid. Mucin induced noticeable changes in all the parameters studied when compared with growth using glucose, including in the formation of cell clusters, which were easily disorganized with trypsin. Mucin increased adhesion of the bacterium, and modulated the production of extracellular proteins. SDS-PAGE revealed that mucin was not degraded during L. rhamnosus GG growth, suggesting that this bacterium is able to partially use the glucidic moiety of glycoprotein. This study goes some way towards developing an understanding of the metabolic and physiological changes that L. rhamnosus GG undergoes within the human gastrointestinal tract.

• Molecules and Cells
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• 제38권1호
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• pp.14-19
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• 2015

Eph receptors and their ligands, ephrins, represent the largest group of the receptor tyrosine kinase (RTK) family, and they mediate numerous developmental processes in a variety of organisms. Ephrins are membrane-bound proteins that are mainly divided into two classes: A class ephrins, which are linked to the membrane by a glycosylphosphatidylinositol (GPI) linkage, and B class ephrins, which are transmembrane ligands. Based on their domain structures and affinities for ligand binding, the Eph receptors are also divided into two groups. Trans-dimerization of Eph receptors with their membrane-tethered ligands regulates cell-cell interactions and initiates bidirectional signaling pathways. These pathways are intimately involved in regulating cytoskeleton dynamics, cell migration, and alterations in cellular dynamics and shapes. The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling. In this review, we present an in-depth overview of the structure, mechanisms, cell signaling, and functions of EphB/ephrinB in cell adhesion and migration.

• Molecules and Cells
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• 제28권3호
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• pp.183-188
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• 2009

TSAd/Lad is a T cell adaptor molecule involved in $p56^{lck}$-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the $p56^{lck}$ proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as $Ca^{2+}$ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

• Journal of Periodontal and Implant Science
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• 제48권5호
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• pp.284-294
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• 2018

Purpose: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. Methods: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha ($TNF{\alpha}$), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor $(NF)-{\kappa}B$ were examined by confocal microscopy. Results: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with $TNF{\alpha}$ induced decreases in the TER and the levels of ZO-1 and nuclear translocation of $NF-{\kappa}B$. These $TNF{\alpha}-induced$ changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. Conclusions: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the $TNF{\alpha}-induced$ impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.

• Journal of Microbiology and Biotechnology
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• 제26권6호
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• pp.1124-1131
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• 2016

In this study, the global proteome of the IPEC-J2 cell line was evaluated using ultra-high performance liquid chromatography coupled to a quadrupole Q Exactive^™ Orbitrap mass spectrometer. Proteins were isolated from highly confluent IPEC-J2 cells in biological replicates and analyzed by label-free mass spectrometry prior to matching against a porcine genomic dataset. The results identified 1,517 proteins, accounting for 7.35% of all genes in the porcine genome. The highly abundant proteins detected, such as actin, annexin A2, and AHNAK nucleoprotein, are involved in structural integrity, signaling mechanisms, and cellular homeostasis. The high abundance of heat shock proteins indicated their significance in cellular defenses, barrier function, and gut homeostasis. Pathway analysis and annotation using the Kyoto Encyclopedia of Genes and Genomes database resulted in a putative protein network map of the regulation of immunological responses and structural integrity in the cell line. The comprehensive proteome analysis of IPEC-J2 cells provides fundamental insights into overall protein expression and pathway dynamics that might be useful in cell adhesion studies and immunological applications.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1719-1722
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• 2012

The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

• 생명과학회지
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• 제24권12호
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• pp.1276-1283
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• 2014

조직의 구조 안정성을 유지하는 세포 사이 연접복합체는 multi-PDZ domain protein 1 (MUPP1)을 포함하여 50종류 이상의 단백질로 이루어져 있다. MUPP1은 13개의 PDZ 도메인을 가지는 단백질로서 막경유(transmembrane) 단백질과 세포골격단백질이나 신호단백질 사이에서 scaffold로 작용한다고 알려져 있지만, MUPP1이 어떻게 세포막인접 단백질들을 연결하고 구조 안정화에 기여하는지에 대해 아직 명확히 밝혀지지 않았다. 본 연구에서 MUPP1의 PDZ 도메인과 상호 작용하는 단백질을 규명하기 위하여 효모 two-hybrid 방법을 이용, cell adhesion molecule 1 (Cadm1; SynCAM1, Necl-2 또는 TSLC1로도 알려짐)이 MUPP1과 결합하는 것을 확인하였다. Cadm1은 MUPP1의 2번째 PDZ 도메인과 결합하며, Cadm1의 C-말단에 존재하는 II 형 PDZ-결합모티프(-Y-F-I)가 MUPP1과의 결합에 필수적임을 확인하였다. 또한 MUPP1은 다른 Cadm family 단백질들인 Cadm2, Cadm3, 그리고 Cadm4와도 결합하며, 이러한 단백질간 결합은 glutathione S-transferase (GST) pull-down assay와 공동면역침강으로도 추가 확인하였다. 생쥐의 뇌 파쇄액을 MUPP1 항체로 면역침강하였을 때 Cadm1과 Cadm4가 같이 침강하였다. 이러한 결과들은 MUPP1이 세포 사이 연접에서 Cadms와 세포골격 단백질 사이를 연결한다는 것을 시사한다.

• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1175-1182
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• 2021

We investigated the effect of bovine lactoferricin (Lfcin-B), a peptide derived from bovine lactoferrin, on activation of intestinal epithelial cells in IEC-6 intestinal cell, and protection against in vivo rotavirus (RV) infection. Treatment with Lfcin-B significantly enhanced the growth of IEC-6 cells and increased their capacity for attachment and spreading in culture plates. Also, Lfcin-B synergistically augmented the binding of IEC-6 cells to laminin, a component of the extracellular matrix (ECM). In the analysis of the intracellular mechanism related to Lfcin-B-induced activation of IEC-6 cells, this peptide upregulated tyrosine-dependent phosphorylation of focal adhesion kinase (FAK) and paxillin, which are intracellular proteins associated with cell adhesion, spreading, and signal transduction during cell activation. An experiment using synthetic peptides with various sequences of amino acids revealed that a sequence of 9 amino acids (FKCRRWQWR) corresponding to 17-25 of the N-terminus of Lfcin-B is responsible for the epithelial cell activation. In an in vivo experiment, treatment with Lfcin-B one day before RV infection effectively prevented RV-induced diarrhea and significantly reduced RV titers in the bowels of infected mice. These results suggest that Lfcin-B plays meaningful roles in the maintenance and repair of intestinal mucosal tissues, as well as in protecting against intestinal infection by RV. Collectively, Lfcin-B is a promising candidate with potential applications in drugs or functional foods beneficial for intestinal health and mucosal immunity.

• BMB Reports
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• 제47권12호
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• pp.655-659
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• 2014

Integrin-mediated cell adhesion is important for development, immune responses, hemostasis and wound healing. Integrins also function as signal transducing receptors that can control intracellular pathways that regulate cell survival, proliferation, and cell fate. Conversely, cells can modulate the affinity of integrins for their ligands a process operationally defined as integrin activation. Analysis of activation of integrins has now provided a detailed molecular understanding of this unique form of "inside-out" signal transduction and revealed new paradigms of how transmembrane domains (TMD) can transmit long range allosteric changes in transmembrane proteins. Here, we will review how talin and mediates integrin activation and how the integrin TMD can transmit these inside out signals.