• Bulletin of the Korean Chemical Society
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• 제25권7호
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• pp.1055-1060
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• 2004

A new inhibitor for peptidylprolyl cis-trans isomerase (PPIase) has been isolated from Ganoderma lucidum and purified to homogeneous state by organic solvent extraction. The purified PPIase inhibitor (GPI) is assumed to be a membrane-associated glycoprotein. GPI inhibits specifically the bovine brain PPIase, a cyclophilin, and has no effect on the FKBP activity. The results of our chemical modification study of GPI indicate the presence of Lys residue(s) at or near its binding site. Like CsA-cyclophilin complex, GPI-bovine brain PPIase complex strongly inhibits the calcineurin activity in vitro, suggesting the possible involvement of GPI in immunomodulating pathway by the formation of PPIase-inhibitor-calcineurin complex.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• Mycobiology
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• 제37권3호
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• pp.161-170
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• 2009

Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC(protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The $Ca^{2+}$/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1835-1842
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• 2020

Ergosterol, an essential constituent of membrane lipids of yeast, is distributed in both the cell membrane and intracellular endomembrane components such as vacuoles. Honokiol, a major polyphenol isolated from Magnolia officinalis, has been shown to inhibit the growth of Candida albicans. Here, we assessed the effect of honokiol on ergosterol biosynthesis and vacuole function in C. albicans. Honokiol could decrease the ergosterol content and upregulate the expression of genes related with the ergosterol biosynthesis pathway. The exogenous supply of ergosterol attenuated the toxicity of honokiol against C. albicans. Honokiol treatment could induce cytosolic acidification by blocking the activity of the plasma membrane Pma1p H+-ATPase. Furthermore, honokiol caused abnormalities in vacuole morphology and function. Concomitant ergosterol feeding to some extent restored the vacuolar morphology and the function of acidification in cells treated by honokiol. Honokiol also disrupted the intracellular calcium homeostasis. Amiodarone attenuated the antifungal effects of honokiol against C. albicans, probably due to the activation of the calcineurin signaling pathway which is involved in honokiol tolerance. In conclusion, this study demonstrated that honokiol could inhibit ergosterol biosynthesis and decrease Pma 1p H+-ATPase activity, which resulted in the abnormal pH in vacuole and cytosol.

• 치위생과학회지
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• 제15권4호
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• pp.488-494
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• 2015

치주인대세포의 효과적인 조절은 성공적인 치주 조직 재생에 중요한 역할을 한다. NFATc1의 활성화가 골모세포에서 분화를 자극하지만, 치주인대세포가 골모세포로 분화하는 과정에서 NFATc1의 역할은 아직 보고되지 않았다. 본 연구는 hPDLCs가 골모세포로 분화하는 동안 NFATc1의 mRNA의 발현과 단백질 발현이 유도됨을 처음으로 확인하였다. CsA에 의한 NFATc1의 억제는 세포증식을 감소시켰다. 게다가, CsA를 처리한 결과, 분화표지자, ALP activity 및 광화결정형성을 감소시켰다. 이러한 연구 결과는 NFATc1이 치주 재생을 위한 골모세포 분화에 중요한 조절자 역할을 할 수 있을 것으로 생각된다.

• Mycobiology
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• 제43권2호
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• pp.150-156
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• 2015

2',4'-Dihydroxychalcone (2',4'-DHC) was identified from a heat shock protein 90 (Hsp90)-targeting library as a compound with Hsp90 inhibitory and antifungal effects. In the presence of 2',4'-DHC ($8{\mu}g/mL$), radial growth of Aspergillus fumigatus was inhibited 20% compared to the control, and green pigmentation was completely blocked. The expression of the conidiation-associated genes abaA, brlA, and wetA was significantly decreased (approximately 3- to 5-fold) by treatment with 2',4'-DHC. The expression of calcineurin signaling components, cnaA and crzA, was also significantly reduced. The inhibitory effects of 2',4'-DHC on metabolic activity and mycelial growth were significantly enhanced by combination treatment with itraconazole and caspofungin. Docking studies indicated that 2',4'-DHC bind to the ATPase domain of Hsp90. These results suggest that 2',4'-DHC act as an Hsp90-calcinurin pathway inhibitor.

• Journal of Plant Biotechnology
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• 제39권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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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.

• 생명과학회지
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• 제33권5호
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• pp.445-454
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• 2023

백발화는 자외선, melanin 세포 자극 호르몬(α-MSH), 줄기 세포 인자 성장인자(SCF), Wnt 및 endothelin-1 (ET-1)에 의하여 활성화되는 melanogenesis를 조절하는 신호 전달 경로가 제대로 작동하지 못하여 나타난 결과이다. 백발화를 예방하기 위하여, tyrosinase, tyrosine hydroxylase, tyrosinase-related protein (TRP)-1, TRP-2 및 microphthalmia-associated transcription factor (MITF)에 의하여 조절되는 melanogenesis를 자극하는 효과적인 합성 및 천연 화합물이 있다. 이러한 화합물은 백발화 예방을 위한 잠재성을 지니고 있다. 이 기사는 melanogenesis와 백발화와 관련된 신호 전달 경로에서 최근의 진전뿐 만 아니라 백발화의 문제를 해결하기 위한 핵심적인 전략에 대해 기술한다. 특히, 이글에서는 catalase 및 methionine sulfoxide reductase를 조절하는 항산화제, resveratrol, fisetin, quercetin 및 ginsenoside와 같은 sirtuin (SIRT) 1 activator와 같은 melanin 생성을 촉진하는 잠재적으로 효과적인 치료제에 대하여 설명한다. 또한 estrogen, androgen, progesterone 및 dihydrotestosterone를 포함하는 telomerase 발현 및 activator 뿐만 아니라, corticosteroids, calcineurin restrainer 및 palmitic acid methyl ester와 같은 백반증 억제제에 대하여 논의한다. 더불어 latanoprost, erlotinib, imatinib, tamoxifen, 및 levodopa와 같은 백발화를 억제할 수 있는 화합물에 대해서도 탐구한다. 결론적으로 이 기사는 모발 백발화와 관련된 melanin 생성을 촉진시키는 화합물에 대한 최근의 연구동향을 고찰한다.

• Molecules and Cells
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• 제20권3호
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• pp.339-347
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• 2005

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.