• 생명과학회지
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• 제13권3호
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• pp.314-323
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• 2003

지금까지 estrogen 호르몬이 유방암의 발생과 진전에 관여한다는 사실을 뒷받침 할 수 있는 여러 가지 증거가 제시되어 왔지만, 암화에 관여하고 있는 estrogen의 분자생물학적 작용기전에 대해서는 아직 명확히 알려져 있지 않다. 유방암 세포의 발암현상은 다양한 핵 수용체들과 이들 각각의 신호전달경로들 사이의 기능적 상호교류 (Functional Cross-talk)에 의해 조절되는 것으로 추측되고 있다. 그러므로, 유방암세포의 성장과 증식에 관여하는 신호전달경로중에서 estrogen의 작용을 조절할 수 있는 핵 수용체를 밝혀내고, 이러한 수용체와 estrogen receptor사이에 어떠한 기능적 상호교류가 일어나는지를 규명하는 것은 암화와 관련된 estrogen의 분자생물학적 작용기전을 이해하는 데 중요한 진전을 가져올 수 있다. 따라서 본 연구의 목적은 유방암세포 내에서 estrogen의 작용이 xenobiotic nuclear receptor에 의해 조절되는지를 규명하기 위하여, 두 종류의 유방암세포인 estrogen receptor가 발현되는 MCF-7 세포와 ER의 발현이 일어나지 않는 MDA-MB-231세포를 배양하여, 에스트로겐에 의해 전사가 촉진되는 보고유전자의 발현이 CAR, SXR, 그리고 PPAR${\gamma}$에 의해서 어떻게 영향을 받는지를 조사하고 그 결과를 간암세포에서의 반응과 비교 분석하였다. 최근에 보고된 연구결과와 일치하게, xenobiotic nuclear receptor가 간세포에서 일어나는 에스트로겐 수용체의 신호전달경로에 영향을 줄 수 있음을 확인하였다. PPAR${\gamma}$를 제외한 핵 수용체 CAR와 SXR은 ER의 전사활성 효과를 현저하게 또는 어느 정도 각각 감소시켰다. Hep G2세포에서와는 달리 유방암세포에서는 조사된 세가지의 xenobiotic 핵 수용체가 ER의 전사활성에 그다지 영향을 미치지 않거나 유방암세포의 종류와 각각의 수용체에 따라서 다소 촉진하는 경향을 나타내었다. MCF-7 세포에서는 CAR와 PPAR${\gamma}$을 제외한 SXR이 ER의 transactivation 효과를 약간 촉진한 반면 MDA-MB-231세포는 SXR을 제외한 CAR와 PPAR${\gamma}$에 의해 ER의 transactivation 효과가 약간 증가되는 경향을 보였다. 이러한 결과는 유방암세포에서는 CAR, SXR, PPAR${\gamma}$과 같은 xenobiotic nuclear receptor에 의한 ER transactivation 효과가 간암세포와는 다르게 나타나며, 유방암의 종류에 따라서 endogenous CAR, SXR, PPAR${\gamma}$수용체가 다르게 발현됨으로써 이들에 대한 반응이 서로 상이한 특징을 나타낼 수 있을 것으로 사료된다. 따라서 estrogen receptor에 의해 매개되는 estrogn의 전사활성조절기전이 표적세포에 따라 다른 경로를 포함 할 수 있음을 시사한다.

• Restorative Dentistry and Endodontics
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• 제31권3호
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• pp.203-214
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• 2006

치수는 상아질로 둘러싸인 간엽조직으로 다양한 세포와 기저 물질들로 구성되어 있으며 혈관과 신경조직이 분포되어 있다. 치수의 염증은 조직의 분해를 야기하며 이는 Matrix Metalloproteinase에 의해 세포 외 기질의 분해가 촉진되어 병적인 과정을 거치게 된다. 이에 Lipopolysaccharide에 의한 MMP와 inflammatory cytokine의 유도와 peroxisome proliferator-activated receptors (PPAR)에 의한 염증매개 물질의 조절에 대해 알아보고자 하였다. 사람의 치수세포를 다양한 LPS농도에 노출시킨 후 24시간째 MMP-2, MMP-9의 변화를 보고 LPS에 의해 자극된 치수세포에서 ICAM-1, VCAM-1, $IL-1{\beta},\;TNF-{\alpha}$의 분비가 증가됨을 알 수 있었다. 또한 Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})$와 $PPAR{\gamma}$ agonist인 rosiglitazone를 LPS로 자극된 치수세포에 처리하였을 때 48시간째 MMPs와 Adhesion molecules, cytokines의 감소를 확인하였다. 이로써 사람의 치수세포에서 $PPAR{\gamma}$가 가지는 항 염증효과에 대해 지속적 인 연구가 필요할 것으로 사료된다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XIII)
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• pp.11-11
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• 2003

• 대한약리학회지
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• 제32권2호
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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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• 제32권8호
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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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• 제27권11호
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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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• 제36권2호
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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.

• 대한의생명과학회지
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• 제12권2호
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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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• 제19권2호
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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.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2003년도 추계학술대회초록집
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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)