• Journal of Life Science
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• v.13 no.3
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• pp.314-323
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• 2003

The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR, SXR, and PPAR${\gamma}$ on the transcriptional activity of estrogen receptor in human breast cancer cell lines and compare with those in human hepatoma cell line. Two different breast cancer cell lines, MCF-7 and MDA-MB-231 were cultured and effects of CAR, SXR, and PPAR${\gamma}$ on the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited ER-mediated transactivation and SXR repressed modestly whereas the PPAR${\gamma}$ did not repress the ER-mediated transactivation. However, in breast cancer cells neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they tend to increase the transactivation depending on the cell type and xenobiotic nuclear receptors. In MCF-7, SXR but neither CAR nor PPAR${\gamma}$ slightly increased ER-mediated transactivation whereas in MDA-MB-231, CAR and PPAR${\gamma}$ but not SXR tend to increase the transactivation of the reporter gene. These results indicate that the effects of ER cross-talk by the CAR, SXR, and PPAR${\gamma}$ , are different in breast cancer cells from hepatoma cells. In conclusion, the transcriptional regulation by estrogen can involve different cross-talk interaction between estrogen receptor and xenobiotic nuclear receptors depending on the estrogen target cells.

• Restorative Dentistry and Endodontics
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• v.31 no.3
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• pp.203-214
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• 2006

Dental pulp is a loose, mesenchymal tissue almost entirely enclosed in the dentin. It consists of cells, ground substance, and neural and vascular supplies. Damage to the dental pulp by mechanical, chemical, thermal, and microbial irritants can provoke various types of inflammatory response. Pulpal inflammation leads to the tissue degradation, which is mediated in part by Matrix metalloproteinase leads to accelerate extracellular matrix degradation with pathological pathway We have now investigated the induction of MMPs and inflammatory cytokines by Lipopolysaccharide (LPS) control of inflammatory mediators by peroxisome proliferator-activated receptors (PPARs). Human dental pulp cells exposed to various concentrations of LPS ($1-10{\mu}g/ml$) revealed elevated levels of MMP-2 and MMP-9 at 24 hrs of culture. LPS also stimulated the production of ICAM-1, VCAM-1, $IL-1{\beta},\;and\;TNF-{\alpha}$. Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})\;and\;PPAR{\gamma}$ agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of $Ad/PPAR{\gamma}$ was higher than that of $PPAR{\gamma}$ agonist. These result offer new insights in regard to the anti-inflammatory potential of $PPAR{\gamma}$ in human dental pulp cell.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.11-11
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• 2003

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.151-158
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• 1996

Following the subcutaneous administration of $R(-)N^6-(2-phenylisopropyl)adenosine(600\;nmol/kg/hr)$ to rats for 1 week using t$Alzet^{\circledR}$ mini-osmotic pumps, $A_1$ adenosine receptor functions were determined using $[^3H]DPCPX$ binding, $[^{35}S]GTP_{\gamma}S$ binding, and adenylyl cyclase assays. $A_1$ adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the $A_1$ adenosine receptor-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of $A_1$ adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of $A_1$ adenosine receptor molecules. It is also suggested that the determination of stimulation of $[^{35}S]GTP_{\gamma}S$ binding to G proteins is a suitable tool in studying the receptor regulation including desensitization

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2717-2721
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1099-1105
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• 2004

The peroxisome proliferator-activated receptors (PPARs) are a primary regulator of lipid metabolism. Potency for activation of PPAR$\gamma$, one of a subfamily of PPARs, particularly mirrors glucose lowering activity. We prepared thiazolidinediones featuring benzoxazole moiety for subtype selective PPAR$\gamma$ activators. 5-[4-[2-(Benzoxazol-2-yl-alkylamino)ethoxy]benzyl]thiazolidine-2,4-diones have been prepared by Mitsunobu reaction of benzoxazolylalkylaminoethanol 8 and hydroxybenzylthiazolidinedione 6 and their activities were evaluated. Most compounds tested were identified as potent PPAR$\gamma$ agonists.

• BMB Reports
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• v.36 no.2
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• pp.207-213
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• 2003

Peroxisome proliferator-activated receptors (PPARs) are orphan nuclear hormone receptors that are known to control the expression of genes that are involved in lipid homeostasis and energy balance. PPARs activate gene transcription in response to a variety of compounds, including hypolipidemic drugs. Most of these compounds have high affinity to the ligand-binding domain (LBD) of PPARs and cause a conformational change within PPARs. As a result, the receptor is converted to an activated mode that promotes the recruitment fo co-activators such as the steroid receptor co-activator-1 (SRC-1). Based on the activation mechanism of PPARs (the ligand binding to $PPAR{\gamma}$ induces interactions of the receptor with transcriptional co-activators), we performed Western blot and ELISA. These showed that the indomethacin, a $PPAR{\gamma}$ ligand, increased the binding between $PPAR{\gamma}$ and SRC-1 in a ligand dose-dependent manner. These results suggested that the in vitro conformational change of $PPAR{\gamma}$ by ligands was also induced, and increased the levels of the ligand-dependent interaction with SRC-1. Collectively, we developed a novel and useful ELISA system for the mass screening of $PPAR{\gamma}$ ligands. This screening system (based on the interaction between $PPAR{\gamma}$ and SRC-1) may be a promising system in the development of drugs for metabolic disorders.

• Biomedical Science Letters
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• v.12 no.2
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• pp.113-118
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• 2006

Major pelvic ganglia (MPG) in rats are an unique autonomic ganglia, containing both sympathetic and parasympathetic neurons related with the function of bladder, penis and bowel. It has been widely known that ionotropic $GABA_A$ receptors are the molecular target of $\gamma$-aminobutric acid (GABA), a major inhibitory neurotransmitter in central nervous system. However, their functions and regulations of $GABA_A$ receptors expressed in autonomic ganglia have been poorly understood. 1 examined the modulatory role of adenylyl cyclase (AC) and protein kinase A(PKA) on $GABA_A$-induced inward currents in the neurons of rat MPG. $GABA_A$ receptors were identified using immunofluorescent labeling in the rat major pelvic ganglion. Electrophysiological experiments were performed to record the activities of $GABA_A$ receptors. $GABA_A$ receptors were expressed only in sympathetic neurons. GABA induced marked inward currents in a concentration-dependent manner. Mucimol ($5{\mu}M$), a $GABA_A$ receptor agonist induced inward currents were significantly reduced in the presence of SQ 225361 $20{\mu}M$, a AC inhibitor and myristoylated PKA inhibitor 100 nM. In addition, forskolin ($1{\mu}M$), AC activator, augmented the GABA induced currents. The activation of AC/PKA-dependent pathway could involve in the regulation $GABA_A$ receptors, expressed only in sympathetic neurons of rat MPG. These findings are helpful for the better understanding the function of various pelvic organs innervated by MPG.

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.208-214
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• 2009

Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of the nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genome-wide micro array analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that $RXR{\alpha}$ is highly expressed in Th2 cells. Overexpression of $RXR{\alpha}$ in a Jurkat human T cell line induced IL4 but not IFN-${\gamma}$ gene expression, suggesting that $RXR{\alpha}$ plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation is influenced by differential regulation of nuclear receptors and coregulators.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.11-11
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• 2003

Peroxisome proliferator-activated receptor (PPAR) is nuclear hormone receptors that can be activated by a variety of compounds. Two PPAR gamma isoforms are expressed at the protein level in mouse, gamma 1 and gamma 2. And PPAR gamma is intimately associated with cell differentiation and proliferation[1]. So aim of this study, investigated where express PPAR gamma in mouse gastric cancer tissues, including human gastric cancer cell lines and expression pattern of PPAR gamma. (omitted)