• Toxicological Research
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• 제35권4호
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• pp.303-310
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• 2019

We are exposed to numerous xenobiotic electrophiles on a daily basis through the environment, lifestyle, and dietary habits. Although such reactive species have been associated with detrimental effects, recent accumulated evidence indicates that xenobiotic electrophiles appear to act as signaling molecules. In this review, we introduce our findings on 1) activation of various redox signaling pathways involved in cell proliferation, detoxification/excretion of electrophiles, quality control of cellular proteins, and cell survival during exposure to xenobiotic electrophiles at low concentrations through covalent modification of thiol groups in sensor proteins, and 2) negative regulation of reactive sulfur species (RSS) in the modulation of redox signaling and toxicity caused by xenobiotic electrophiles.

• International Journal of Oral Biology
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• 제43권4호
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• pp.171-175
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• 2018

Quorum sensing (QS) is a cell density-dependent communication mechanism between bacteria through small signaling molecules. When the number of QS signaling molecules reaches a threshold, they are transported back into the cells or recognized by membrane-bound receptors, triggering gene expression which affects various phenotypes including bioluminescence, virulence, adhesion, and biofilm formation. These phenotypes are beneficial for bacterial survival in harsh environments. This review summarizes the application of QS inhibitors for control of biofilm formation and virulence expression of periodontal pathogens.

• Interdisciplinary Bio Central
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• 제4권4호
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• 동의생리병리학회지
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• 제22권2호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권6호
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• pp.530-543
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• 2006

Adeonoid cystic carcinoma (ACC) is one of the most common malignant tumors of salivary glands. It is characterized by a relentless regrowth especially around nerve tissues and a high rate of hematogenous distant metastasis. Clinically most deaths from salivary ACC are caused by delayed lung metastases that are resistant to conventional chemotherapy. So, knowledge of cellular and molecular properties that influence the dissemination of metastatic tumor cells, is important for new treatment strategies of metastatic lesions. We determined expressions of angiogenic signaling molecules microvessel density (MVD) using surgical specimens of human salivary ACC. Protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, activated VEGFR-2, and human CD31 were assessed in 20 cases of salivary ACC by immunohistochemical staining. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for antibodies of VEGF, VEGFR-2, and activated VEGFR-2. The overall percentages of the 20 specimens expressing VEGF, VEGFR-2, activated VEGFR-2 were 90, 95, and 95%, respectively. Immunoreactivities of the biomarkers in salivary ACC were higher than those in normal salivary gland. Furthermore, immune-related cells as well as tumor cells expressed VEGF/VEGFR-2. Microvessel density of salivary ACC was higher than that of normal salivary gland (P<0.05). Taken together, angiogenic signaling molecules are actively expressed in salivary ACC. And we suggest that these molecules may have critical role in the hematogenous spread of salivay ACC, which has a propensity for delayed lung metastasis. Therefore, these biomarkers can be molecular targets for therapy of metastasis of salivary ACC.

• Archives of Pharmacal Research
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• 제29권2호
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• pp.113-122
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• 2006

Among the effector molecules connected with the group of cell surface receptors, Ras proteins have essential roles in transducing extracellular signals to diverse intracellular events, by controlling the activities of multiple signaling pathways. For over 20 years since the discovery of Ras proteins, an enormous amount of knowledge has been accumulated as to how the proteins function in overlapping or distinct fashions. The signaling networks they regulate are very complex due to their multiple functions and cross-talks. Much attention has been paid to the pathological role of Ras in tumorigenesis. In particular, human tumors very frequently express Ras proteins constitutively activated by point mutations. Up to date, three members of the Ras family have been identified, namely H-Ras, K-Ras (A and B), and N-Ras. Although these Ras isoforms function in similar ways, many evidences also support the distinct molecular function of each Ras protein. This review summarizes differential functions of Ras and highlights the current view of the distinct signaling network regulated by each Ras for its contribution to the malignant phenotypic conversion of breast epithelial cells. Four issues are addressed in this review: (1) Ras proteins, (2) membrane localization of Ras, (3) effector molecules downstream of Ras, (4) Ras signaling in invasion. In spite of the accumulation of information on the differential functions of Ras, much more remains to be elucidated to understand the Ras-mediated molecular events of malignant phenotypic conversion of cells in a greater detail.

• 한국수정란이식학회지
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• 제27권4호
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• pp.211-221
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• 2012

The process of embryo implantation requires physical contact and physiological communication between the conceptus trophectoderm and the maternal uterine endometrium. During the peri-implantation period in pigs, the conceptus undergoes significant morphological changes and secretes estrogens, the signal for maternal recognition of pregnancy. Estrogens secreted from the conceptus act on uterine epithelia to redirect $PGF_2{\alpha}$, luteolysin, secretion from the uterine vasculature to the uterine lumen to prevent luteolysis as well as to induce expression of endometrial genes that support implantation and conceptus development. In addition, conceptuses secrete cytokines, interferons, growth factors, and proteases, and in response to these signals, the uterine endometrium produces hormones, protease inhibitors, growth factors, transport proteins, adhesion molecules, lipid molecules, and calcium regulatory molecules. Coordinated interactions of these factors derived from the conceptus and the uterus play important roles in the process of implantation in pigs. To better understand mechanism of implantation process in pigs, this review provides information on signaling molecules at the conceptus-uterine interface during early pregnancy, including recently reported data reported.

• Journal of Photoscience
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• 제9권2호
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• pp.482-484
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• 2002

UV irradiation activates various intracellular signaling pathways causing cell death in a DNA damage-dependent and an independent manner. As DNA photoproducts, major forms of DNA damage, are maximally formed by UV light at 260-nm, short wavelength UV (UVC) is more harmful than middle wavelength UV (UVB). However, the differences or similarities in responses of DNA damage-independent intracellular signaling molecules to UVB and UVC are not elucidated. We examined activation of signaling molecules towards apoptosis in normal human fibroblastic cells after irradiation with UVB or UVC at a dose generating the equal amount of DNA photoproducts. Both UVB and UVC induced transient phosphorylation of ERK and sustained phosphorylation of p38. Phosphorylation of p53 at Ser15 and at Ser392 residues were also observed, which were inhibited by a phosphoinositide 3-kinase inhibitor, wortmannin. In contrast, an antioxidant N-acetyl-cysteine and a p38 inhibitor SB203580 suppressed only Ser392 phosphorylation, suggesting that UV-induced oxidative stress and p38 activation were involved in the phosphorylation of this site. The apoptic signals such as mitochondrial cytochrome C release and annexin V binding were then observed. Overall, no difference was found in chronological responses of p53, MAPK, and apoptosis between UVB-irradiated and UVC-irradiated cells. These results suggested that DNA damage-independent intracellular signaling molecules similarly responded to UVB and UVC when the equal level of DNA photoproducts were generated.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1731-1735
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• 2013

Objective: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. Methods: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. Results: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. Conclusions: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

• BMB Reports
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• 제44권12호
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• pp.772-781
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• 2011

Branched N-glycans are produced by a series of glycosyltransferases including N-acetylglucosaminyltransferases and fucosyltransferases and their corresponding genes. Glycans on specific glycoproteins, which are attached via the action of glycosyltransferases, play key roles in cell adhesion and signaling. Examples of this are adhesion molecules or signaling molecules such as integrin and E-cadherin, as well as membrane receptors such as the EGF and TGF-${\beta}$ receptors. These molecules also play pivotal roles in the underlying mechanism of a variety of disease such as cancer metastasis, diabetes, and chronic obstructive pulmonary disease (COPD). Alterations in the structures of branched N-glycans are also hall marks and are useful for cancer biomarkers and therapeutics against cancer. This mini-review describes some of our recent studies on a functional glycomics approach to the study of branched N-glycans produced by N-acetylglucosaminyltransferases III, IV, V and IX (Vb) (GnT-III, GnT-IV, V and IX (Vb)) and fucosyltransferase 8 (Fut8) and their pathophysiological significance, with emphasis on the importance of a systems glycobiology approach as a future perspective for glycobiology.