• Proceedings of the PSK Conference
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• 2002.10a
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• pp.306.2-306.2
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• 2002

The main targets for the immunosuppressive calcineurin inhibitors. tacrolimus (FK-506) and cyclosporine A (CsA). have been considered to be activated T cells. but not antigen presenting cells (APCs). In the present study. we examined the effects of these drugs on the MHC-restricted presentation of exogenously added antigen. ovalbumin (OVA). in dendritic cells (DCs). Particulate form of OVA was efficiently captured. processed and presented on class I MHC molecules (cross-presentation) as well as on class II MHC molecules. (omitted)

• Korean Journal of Food Science and Technology
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• v.45 no.4
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• pp.508-514
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• 2013

2Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However, it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model. Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation, similar to INCA-6.

• Journal of Life Science
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• v.23 no.1
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• pp.1-7
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• 2013

Understanding salt tolerance mechanisms is important for the increase of crop yields, and so, several screening approaches were developed to identify plant genes which are involved in salt tolerance of plants. Here, we transformed the Arabidopsis cDNA library into a salt-sensitive calcineurin (CaN)-deficient ($cnb{\Delta}$) yeast mutant and isolated the colonies which can suppress salt-sensitive phenotype of $cnb{\Delta}$ mutant. Through this functional complementation screen, a total of 34 colonies functionally suppressed the salt-sensitive phenotype of $cnb{\Delta}$ yeast cells, and sequencing analysis revealed that these are 9 genes, including CaS, AtSUMO1 and AtHB-12. Among these genes, the ectopic expression of CaS gene increased salt tolerance in yeast, and CaS transcript was up-regulated under high salinity conditions. CaS-antisense transgenic plants showed reduced root elongation under 100 mM NaCl treatment compared to the wild type plant, which survived under 150 mM NaCl treatment, whereas CaS-antisense transgenic plant leaves turned yellow under 150 mM NaCl treatment. These results indicate that the expression of CaS gene is important for stress tolerance in yeast and plants.

• Journal of Life Science
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• v.33 no.5
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• pp.445-454
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• 2023

Hair graying is the result of a malfunction in the signaling pathways that control melanogenesis, and it is activated by UV light, melanocyte-stimulating hormone (MSH), stem cell factor (SCF), Wnt, and endothelin-1 (ET-1). To prevent hair graying, synthetic and natural compounds can be used to stimulate melanogenesis effectively under the control of tyrosinase, tyrosine hydroxylase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF). This article describes a crucial strategy to resolve the problem of hair graying, as well as recent advances in the signaling pathway related to melanogenesis and hair graying. In particular, the article reviews potentially effective therapeutic agents that promote melanogenesis, such as antioxidants that modulate catalase, methionine sulfoxide reductase, and sirtuin 1 (SIRT1) activators including resveratrol, fisetin, quercetin, and ginsenoside. It also discusses vitiligo inhibitors, such as corticosteroids, calcineurin inhibitors, and palmitic acid methyl ester, as well as activators of telomerase expression and activity, including estrogen, androgen, progesterone, and dihydrotestosterone. Furthermore, it explores compounds that can inhibit hair graying, such as latanoprost, erlotinib, imatinib, tamoxifen, and levodopa. In conclusion, this article focuses on recent research trends on compounds that promote melanin production related to hair graying.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• BMB Reports
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• v.49 no.6
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• pp.303-304
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• 2016

Myoblast fusion is important for skeletal muscle formation. Even though the knowledge of myoblast fusion mechanism has accumulated over the years, the initial signal of fusion is yet to be elucidated. Our study reveals the novel function of a phosphatidylserine (PS) receptor, stabilin-2 (Stab2), in the modulation of myoblast fusion, through the recognition of PS exposed on myoblasts. During differentiation of myoblasts, Stab2 expression is higher than other PS receptors and is controlled by calcineurin/NFAT signaling on myoblasts. The forced expression of Stab2 results in an increase in myoblast fusion; genetic ablation of Stab2 in mice causes a reduction in muscle size, as a result of impaired myoblast fusion. After muscle injury, muscle regeneration is impaired in Stab2-deficient mice, resulting in small myofibers with fewer nuclei, which is due to reduction of fusion rather than defection of myoblast differentiation. The fusion-promoting role of Stab2 is dependent on its PS-binding motif, and the blocking of PS-Stab2 binding impairs cell-cell fusion on myoblasts. Given our previous finding that Stab2 recognizes PS exposed on apoptotic cells for sensing as an "eat-me" signal, we propose that PS-Stab2 binding is required for sensing of a "fuse-me" signal as the initial signal of myoblast fusion.

• Journal of Plant Biotechnology
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• v.39 no.2
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• pp.106-113
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• 2012

Glycolysis is responsible for the conversion of glucose into pyruvate and for supplying reducing power and several metabolites. Fructose-1,6-bisphosphate aldolase (AtFBA1), a central enzyme in the glycolysis pathway, was isolated by functional complementation of the salt-sensitive phenotype of a calcineurin (CaN)-deficient yeast mutant. Under high salinity conditions, aldolase activity and the concentration of NADH were compromised. However, expression of AtFBA1 maintained aldolase activity and the NADH level in yeast cells. AtFBA1 shares a high degree of sequence identity with known class I type aldolases, and its expression was negatively regulated by stress conditions including NaCl. The fusion protein GFP-AtFBA1 was localized in the cytosol of Arabidopsis protoplasts. The seed germination and root elongation of AtFBA1 knock-out plants exhibited sensitivity to ABA and salt stress. These results indicate that AtFBA1 expression and aldolase activity is important for stress tolerance in yeast and plants.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7439-7444
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• 2013

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.483-489
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• 2009

Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.126-133
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• 2020

Homer proteins are scaffold proteins that regulate calcium (Ca²⁺) signaling by modulating the activity of multiple Ca²⁺ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2/Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2^-/-) and Homer3 (Homer3^-/-) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.