• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.29-29
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• 2003

Compartmentation of intracellular signaling pathways serves as an important mechanism conferring the specificity of G protein-coupled receptor (GPCR) signaling. In the heart, stimulation of $\beta$$_2$-adrenoceptor ($\beta$$_2$-AR), a prototypical GPCR, activates a tightly localized protein kinase A (PKA) signaling, which regulates substrates at cell surface membranes, bypassing cytosolic target proteins (eg, phospholamban). Although a concurrent activation of $\beta$$_2$-AR-coupled $G_{i}$ proteins has been implicated in the functional compartmentation of PKA signaling, the exact mechanism underlying the restriction of the $\beta$$_2$-AR-PKA pathway remains unclear. In the present study, we demonstrate that phosphatidylinositol 3-kinase (PI3K) plays an essential role in confining the $\beta$$_2$-AR-PKA signaling. Inhibition of PI3K with LY294002 or wortmannin enables $\beta$$_2$-AR-PKA signaling to reach intracellular substrates, as manifested by a robust increase in phosphorylation of phospholamban, and markedly enhances the receptor-mediated positive contractile and relaxant responses in cardiac myocytes. These potentiating effects of PI3K inhibitors are not accompanied by an increase in $\beta$$_2$-AR-induced cAMP formation. Blocking $G_{i}$ or $G_{$\square$$\square$}$ signaling with pertussis toxin or $\beta$ARK-ct, a peptide inhibitor of $G_{$\square$$\square$}$, completely prevents the potentiating effects induced by PI3K inhibition, indicating that the pathway responsible for the functional compartmentation of $\beta$$_2$-AR-PKA siglaling sequentially involves $G_{i}$, $G_{$\square$$\square$}$, and PI3K. Thus, PI3K constitutes a key downstream event of $\beta$$_2$-AR- $G_{i}$ signaling, which confines and negates the concurrent $\beta$$_2$-AR/Gs-mediated PKA signaling.gnaling.

• Journal of Chest Surgery
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• 제39권11호
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• pp.805-809
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• 2006

배경: Transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) 단백질의 과발현이 폐기포 조직의 형성에 관여할 수 있다는 연구 결과를 본 연구팀은 발표한 바 있다. 이와 관련하여 폐기포벽에서 발견되는 섬유화에 관계될 것으로 생각되는 Transforming growth factor-beta 1(TGF-${\beta}1$) ligand의 발현의 변화를 보기 위하여 자연기흉 환자에서 폐기포 절제슬로 획득한 폐 기포조직을 면역조직화학적 염색법으로 염색하여 관찰하려 하였다. 대상 및 방법: 36명의 자연기흉의 환자에서 비디오흉강경 폐기포절제술 시 획득된 폐기포조직을 획득하였다. 36명 환자 중 남자가 34명, 여자가 2명이었고 연령은 14세에서 38세였다. 획득된 폐기포조직을 면역조직화학적 염색방법으로 염색하였다. 결과: 36명 중 19예에서 TGF-${\beta}1$ 양성이었고 24예에서는 transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$)가 양성이었다. 19예의 TGF-${\beta}1$ 양성 예 중 15예에서 TGF-${\beta}1RII$에도 양성으로 관찰되었다. 이 같은 양성 변화는 폐기포조직과 정상 폐 조직과의 경계선에서 가장 강하게 관찰되었다. 결론: TGF-${\beta}1$의 과발현은 TGF-${\beta}1RII$ 발현의 변이 여부와 마찬가지로 폐기포벽의 섬유화를 초래하여 폐기포 형성에 영향을 미치는 것으로 생각되며 확실한 규명을 위하여 분자생물학적 및 기타 추가적인 연구가 더 필요할 것으로 생각된다.

• Bulletin of the Korean Chemical Society
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• 제32권6호
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• pp.2008-2014
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• 2011

Serotonin or 5-hydroxytryptamine subtype 2C ($5-HT_{2C}$) receptor belongs to class A amine subfamily of G-protein-coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (${\beta}$2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4949-4954
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• 2015

The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

• 한국발생생물학회지:발생과생식
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• 제24권4호
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• pp.287-296
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• 2020

The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. The present research was aimed to evaluate expression of various molecules associated with adipocyte differentiation and maturation in the epididymal fat of ERαKO mouse at several postnatal ages by using quantitative real-time polymerase chain reaction. The highest transcript levels of all molecules were detected at 12 months of postnatal age, except leptin which the mRNA level was increased at 5 months of age and was unchanged until 12 months of age. The expression levels of CCAAT enhancer binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were decreased at 5 months of age but increased at about 8 months of age. The mRNA levels of Cebp gamma and sterol regulatory element binding transcription factor 1 remained steady until 8 months of age. Continuous increases of transcript levels during postnatal period were found in Cebp beta, estrogen receptor (ER) beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1. The increases of peroxisome proliferator-activated receptor gamma and adiponectin mRNA levels were detected as early as 8 months of age. The levels of fatty acid synthase and resistin transcript at 5 and 8 months of age were lower than that at 2 months of age. These findings show the aberrant expression patterns of genes related to adipocyte differentiation and maturation in the postnatal epididymal fat pad by the disruption of ER alpha function.

• 약학회지
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• 제32권6호
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• pp.428-434
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• 1988

The effects of calcium and calcium antagonist, nifedipine on the adrenergic receptor-stimulated glycogenolysis were investigated in isolated rat hepatocytes. The hepatic glycogenolysis induced by alpha-adrenergic receptor stimulation depended on calcium ions, and beta-adrenergic activation was unrelated to calcium ions. Nifedipine decreased the alpha-adrenergic agonist-induced glucose release significantly and the decrease was depended on calcium ions. The glucose release induced by beta-adrenergic agonist was not inhibited by nifedipine.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.135-135
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• 2003

Bisphenol A (BPA) mimics estrogen and its activity is one third to one quarter that of estradiol. BPA, an ubiquitous environmental contaminent has been shown to cause development reproductive toxicity and carcinogenic effect. BPA may do physiological action through ER${\alpha}$ and ER${\beta}$ which are expressed in central nerve system.(omitted)

• 동의생리병리학회지
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• 제17권1호
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• pp.241-246
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• 2003

Bambusae Caulis in Liquamen(BCL) has been used to relieve the cough and asthma, and remove the phlegm in traditional Oriental medicine. In recent years, it was studied for its antiinflammatory, antiallergenic, immune-modulating, and anticarcinogenic capabilities. This experiment was performed to evaluate the microarray profiles of CD genes in human mast cells before and after BCL treatment. The results are as follows: The expression of 51 of the genes studied was up-regulated in the Bel-treated group; they include the genes coding L apoferritin, beta-2-microglobulin, ferritin light polypeptide, CD63, monocyte chemotactic and activating fact, heme oxygenase 1, CD140a, integrin alpha M, colony stimulating factor 2 receptor, eukaryotic translation elongation factor, CD37, interleukin 18, NADH dehydrogenase 1 beta, CD48, 5-lipoxygenase activating protein, interleukin 4, ribosomal protein L5, GABA(A) receptor-associated protein, beta-tubulin, integrin beta 1, CD162, CD32, lymphotoxin beta, alpha-tublin, integrin alpha L, CD2, CD151, CD331, 90 kDa heat shock protein, CD59, CD3Z, microsomal glutathione S-transferase 2, CD33, CD162R, cyclophilinA, CD84, interleukin 9 receptor, interleukin 11, CD117, CD39-Like 2, and so forth. The expression of 7 of the genes studied was down-regulated in the BCL-treated group; they include the genes coding con, CD238, SCF, CD160, CD231, CD24, and CD130. Consequently, the treatment of BCL on the human mast cells increased the expression of 51 genes and decreased the expression of 7 genes. These data would provide a fundamental basis to the traditional applications of Bambusae Caulis in Liquamen.

• 한국자원식물학회지
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• 제25권6호
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• pp.664-669
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• 2012

The mushroom Coriolusversicolor contains biologically active polysaccharides, most of which belong to the ${\beta}$ glucan group. Diverse physicochemical properties, due to different sources and isolated types of ${\beta}$-glucans, may induce distinct biological activities. Here, we examined the effects of ${\beta}$-glucan from Coriolusversicolor (CVG) on the scavenger receptor B1 (SR-B1) expression and the role of SR-B1 in CVG-induced phagocytosis regulation by using SR-B1-specific shRNA transfected cells. We also examined whether Dectin-1 and CK2 are involved in SR-B1 expression in CVG-treated cells. Our study results showed that CVG increased the SR-B1 expression via Dectin-1 and CK2 in macrophages. However, the inhibition of SR-B1 expression by shRNA did not completely eliminate the effect of CVG on the increase of phagocytosis suggesting that SR-B1 is not essential for CVG-stimulated phagocytosis. This study will contribute to identify CVG's mechanism of action and its use in the development of functional foods.

• Bulletin of the Korean Chemical Society
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• 제29권6호
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• pp.1107-1114
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• 2008

It is important to identify selective ligands for the estrogen receptor subtypes ER$\alpha$ or ER$\beta$ to evaluate them as pharmaceutical targets in breast cancer. To develop ER$\beta$-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ER$\alpha$ vs ER$\beta$. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ER$\beta$/ER$\alpha$ selectivity, respectively. However, their binding affinities to ER$\alpha$ and ER$\beta$ were very low.