• 제목/요약/키워드: Nuclear receptor

검색결과 683건 처리시간 0.029초

Retinoid X Receptor Isoforms $\alpha$ and $\beta$ Differentially Regulate 3,5,3’ -Triiodothyronine- induced Transcription

  • Rhee, Myung-chull
    • Animal cells and systems
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    • 제2권4호
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    • pp.489-493
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    • 1998
  • Various heterodimers of the thyroid hormone receptor (TR) with other nuclear hormone receptors confer a wide range of transcriptional activities on thyroid hormone response elements (TREs) in the presence of the thyroid hormone ($T_3$). The present study analyzed the potential roles of retinoid X receptor (RXR) isoforms $\alpha$ and $\beta$ in $T_3$-mediated transcription on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleo-tides (DR4), using electrophoretic mobility shift assays and transient transfection in CV-1 cells. We demonstrated that RXR$\alpha$ supressed liganded $TR_{\alpha}$-induced transcription while $RXR_{\beta}$ did not although both $TR_{\alpha}/RXR_{\alpha}$ and $TR_{\alpha}/RXR_{\beta}$ heterodimers were the predominant forms bound to the TRE-DR4 in the presence of $T_3$. We further demonstrated using Scatchard analysis that the two heterodimers had similar affinities for the TRE-DR4. All these observations suggest that the TRE-DR4 accomodates different types of TR/RXR heterodimers for a more finely tuned transcriptional response to $T_3$.

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DIFFERENTIATION MECHANISM OF GINSENOSIDES IN CULTURED MURINE F9 TERATOCARCINOMA STEM CELLS

  • Lee H.Y.;Kim S.I.;Lee S.K.;Chung H.Y.;Kim K.W.
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1993년도 학술대회지
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    • pp.127-131
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    • 1993
  • The effects of total ginseng saponin. extracts of Panax ginseng C.A. Meyer, on the differentiation of F9 teratocarcinoma stem cells were studied. F9 stem cells cultured in the presence of ginseng saponin together with dibutyric cAMP became parietal endoderm - like cells. Moreover, the expressions of differentiation marker genes. laminin. type IV collagen. and retinoic acid $receptor-{\beta}(RAR{\beta})$ were increased after treatment of ginseng saponin. Among various ginsenosides purified from crude ginseng saponin, $Rh_1\;and\;Rh_2$ caused the differentiation of F9 cells most effectively. Since ginsenosides and steroid hormone show resemblance in chemical structure. we studied the possibility of the involvement of a steroid receptor in the differentiation process induced by ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarding as a steroid receptor was detected in F9 cells cultured in the medium containing ginseng saponin. Based on these data, we suggest that ginseng saponin, especially ginsenosides $Rh_1\;and\;Rh_2$ cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a steroid receptor or its analogous nuclear receptor.

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형질전환효모를 이용한 내분비계장애물질검색과 Nonylphenol의 Estrogen 유사작용에 대한 DEHP의 상협작용 (Modification of Estrogenic Effect of Nonylphenol Combined with DEHP in Yeast-based Bioassay)

  • 박미선;정해관;박현신;한의식;김종원;엄미옥;정상희;오혜영
    • Toxicological Research
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    • 제17권1호
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    • pp.65-71
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    • 2001
  • The key targets of endocrine disruptors are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. A yeast-based steroid hormone receptor gene trascription assay was previously developed for the evaluation of chemicals with endocrine modulating activity. The yeast transformants used in this assay contain the human estrogen receptor along with the appropriate steroid response elements upstream of the $\beta$-galactosidase reporter gene. We tried to evaluate several natural and synthetic steroids of their potential to interact directly with the steroid receptor. Some putative endocrine disruptors, including nonylphenol, are weakly estrogenic. But the combined treatment oj these chemicals with di-(2-ethylhexyl)phthalate (DEHP) significantly increased the $\beta$-galactosidase activity in the yeast transformant. These results suggest that we also have to consider the synergistic effects of endocrine disruptors. In this study, we showed that yeast-based bioassay is a valuable tool for screening potential endocrine disruptors and quantitative determination of estrogenicity. And the possibility that the estrogen receptor binds multiple environmental chemicals adds another level of complexity to the interaction between the endocrine disruptors and the human hormone system.

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$^{111}In$-Pentetreotide 스캔으로 진단 가능했던 가스트린종을 가진 Zollinger-Ellison 증후군 1예 (A Case of Zollinger-Ellison Syndrome with Gastrinoma Localized by $^{111}In$-Pentetreotide Scan)

  • 정현조;류진숙;김재승;문대혁;정훈용;하현권;이희경
    • 대한핵의학회지
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    • 제33권6호
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    • pp.537-542
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    • 1999
  • In patient with Zollinger-Ellison syndrome, it is difficult to localize gastrinoma because the tumor is frequently small and multiple. However, accurate localization of the tumor is important for the treatment Among various imaging modalities, somatostatin receptor scintigraphy (SRS) has been recognized to be the most sensitive tool for the detection of neuroendocrine tumors such as gastrinomas based on the presence of high-affinity binding sites for somatostatin. Recently, we experienced a case of Zollinger-Ellison syndrome caused by gastrinomas which was localized by SRS. This is the first case report of gastrinoma detected by SRS in Korea. SRS can facilitate tumor detection in patient with Zollinger-Ellison syndrome and should be considered as the first-line diagnostic method in the early course of the disease.

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Effects of Lactobacillus reuteri MG5346 on Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL)-Induced Osteoclastogenesis and Ligature-Induced Experimental Periodontitis Rats

  • Yu-Jin Jeong;Jae-In Jung;YongGyeong Kim;Chang-Ho Kang;Jee-Young Imm
    • 한국축산식품학회지
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    • 제43권1호
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    • pp.157-169
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    • 2023
  • Effects of culture supernatants of Lactobacillus reuteri MG5346 (CS-MG5346) on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis were examined. CS-MG5346 treatment up to 400 ㎍/mL significantly reduced tartrate-resistant acid-phosphatase (TRAP) activity, the phenotype biomarker of osteoclast, without affecting cell viability. CS-MG5346 inhibited the expression of osteoclast specific transcriptional factors (c-fos and nuclear factor-activated T cells c1) and their target genes (TRAP, cathepsin, and matrix metallo-proteinase-9) in a dose-dependent manner (p<0.05). The administration of L. reuteri MG5346 (2×108 CFU/day) for 8 wks significantly improved furcation involvement, but no difference was observed in alveolar bone loss in ligature-induced experimental periodontitis rats. The elevated RANKL/osteoprotegerin ratio, the biomarker of periodontitis, was significantly lowered in the gingival tissue by administration of L. reuteri MG5346 (p<0.05). L. reuteri MG5346 showed excellent stability in simulated stomach and intestinal fluids and did not have antibiotic resistance. Based on the results, L. reuteri MG5346 has the potential to be a promising probiotic strain for oral health.

Inhibitory effects of Oxya chinensis sinuosa ethanol extract on RANKL-induced osteoclast differentiation

  • Ra-Yeong Choi;Bong Sun Kim;Sohyun Park;Minchul Seo;Joon Ha Lee;HaeYong Kweon;In-Woo Kim
    • International Journal of Industrial Entomology and Biomaterials
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    • 제48권1호
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    • pp.13-18
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    • 2024
  • The rice field grasshopper, Oxya chinensis sinuosa (OC), has traditionally been utilized in Korea for various purposes; however, its potential benefits in the context of osteoporosis remain unclear. The results revealed that OC ethanol extract (OCE) significantly inhibited the formation and activity of tartrate-resistant acid phosphatase (TRAP)-positive cells in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated RAW264.7 cells. Furthermore, OCE, at concentrations ranging from 100 to 400 ㎍/mL, demonstrated a dose-dependent reduction in the protein expression of osteoclast-specific markers, including nuclear factor of activated T cell cytoplasmic 1, c-Src, and TRAP, when compared to RANKL stimulation alone. Additionally, OCE significantly inhibited RANKL-induced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) but not the activation of extracellular signal-regulated kinase. Collectively, these results indicate that OCE suppresses osteoclastogenesis by attenuating the phosphorylation of p38 MAPK and JNK. Consequently, these findings suggest that OCE holds promise for the prevention of osteoporosis.

Trichostatin A Protects Liver against Septic Injury through Inhibiting Toll-Like Receptor Signaling

  • Kim, So-Jin;Park, Jin-Sook;Lee, Do-Won;Lee, Sun-Mee
    • Biomolecules & Therapeutics
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    • 제24권4호
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    • pp.387-394
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    • 2016
  • Sepsis, a serious clinical problem, is characterized by a systemic inflammatory response to infection and leads to organ failure. Toll-like receptor (TLR) signaling is intimately implicated in hyper-inflammatory responses and tissue injury during sepsis. Histone deacetylase (HDAC) inhibitors have been reported to exhibit anti-inflammatory properties. The aim of this study was to investigate the hepatoprotective mechanisms of trichostatin A (TSA), a HDAC inhibitor, associated with TLR signaling pathway during sepsis. The anti-inflammatory properties of TSA were assayed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The mice were intraperitoneally received TSA (1, 2 or 5 mg/kg) 30 min before CLP. The serum and liver samples were collected 6 and 24-h after CLP. TSA inhibited the increased production of tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 in LPS-stimulated RAW264.7 cells. TSA improved sepsis-induced mortality, attenuated liver injury and decreased serum TNF-${\alpha}$ and IL-6 levels. CLP increased the levels of TLR4, TLR2 and myeloid differentiation primary response protein 88 (MyD88) protein expression and association of MyD88 with TLR4 and TLR2, which were attenuated by TSA. CLP increased nuclear translocation of nuclear factor kappa B and decreased cytosolic inhibitor of kappa B ($I{\kappa}B$) protein expression, which were attenuated by TSA. Moreover, CLP decreased acetylation of $I{\kappa}B$ kinase (IKK) and increased association of IKK with $I{\kappa}B$ and TSA attenuated these alterations. Our findings suggest that TSA attenuates liver injury by inhibiting TLR-mediated inflammatory response during sepsis.

Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells

  • Huang, Ze-Min;Wu, Jun;Jia, Zheng-Cai;Tian, Yi;Tang, Jun;Tang, Yan;Wang, Ying;Wu, Yu-Zhang;Ni, Bing
    • BMB Reports
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    • 제45권6호
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    • pp.331-336
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    • 2012
  • The retinoid-related orphan nuclear receptor gamma ($ROR{\gamma}$) plays critical roles in regulation of development, immunity and metabolism. As transcription factor usually forms a protein complex to function, thus capturing and dissecting of the $ROR{\gamma}$ protein complex will be helpful for exploring the mechanisms underlying those functions. After construction of the recombinant tandem affinity purification (TAP) plasmid, pMSCVpuro $ROR{\gamma}$-CTAP(SG), the nuclear localization of $ROR{\gamma}$-CTAP(SG) fusion protein was verified. Following isolation of $ROR{\gamma}$ protein complex by TAP strategy, seven candidate interacting proteins were identified. Finally, the heat shock protein 90 (HSP90) and receptor-interacting protein 140 (RIP140) were confirmed to interplay with $ROR{\gamma}$ by co-immunoprecipitation. Interference of HSP90 or/and RIP140 genes resulted in dramatically decreased expression of CYP2C8 gene, the $ROR{\gamma}$ target gene. Data from this study demonstrate that HSP90 and RIP140 proteins interact with $ROR{\gamma}$ protein in a complex format and function as co-activators in the $ROR{\gamma}$-mediated regulatory processes of HepG2 cells.