• Title/Summary/Keyword: Glucocorticoid

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Effect of p16 on glucocorticoid response in a B-cell lymphoblast cell line

  • Kim, Sun-Young;Lee, Kyung-Yil;Jeong, Dae-Chul;Kim, Hak-Ki
    • Clinical and Experimental Pediatrics
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    • v.53 no.7
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    • pp.753-758
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    • 2010
  • Purpose: It has been suggested that p16 has a role in glucocorticoid (GC)-related apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified. We evaluated the relationship between the GC response and p16 expression in a lymphoma cell line. Methods: We used p16 siRNA transfection to construct p16-inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared glucocorticoid receptor (GR) expression, apoptosis, and cell viability between control (p16+NC-37) and p16 siRNA-transfected (p16-NC-37) cells after a single dose of dexamethasone (DX). Results: In both groups, there was a significant increase in cytoplasmic GR expression, which tended to be higher for p16+NC-37 cells than for p16- NC37 cells at all times, and the difference at 18 h was significant (P<0.05). Similar patterns of early apoptosis were observed in both groups, and late apoptosis occurred at higher levels at 18 h when the GR had already been downregulated ($P$<0.05). Cell viability decreased in both groups but the degree of reduction was more severe in p16+NC-37 cells after 18 h ($P$<0.05). Conclusion: These results suggest a relationship between GR expression and cell cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity to DX.

Effect of Bupleuri Radix Aqua-Acupuncture Solution on Immune Response in Mice (시호 약침제제가 생쥐의 면역활성에 미치는 영향)

  • Moon, Jin-Young;Lim, Jong-Kook;Choi, Hey-Kyung;Lee, Yim-Tae;Lee, Hang-Woo;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.30 no.2
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    • pp.115-122
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    • 1999
  • In order to investigate the effects of Bupleuri Radix aqua-acupuncture solution (BRAS) on immuno suppression induced by glucocorticoid, ICR mice were administrated with glucocorticoid (80 mg/kg) for 7 days, and immunized with hapten, methamphetamine-horseradish peroxidase $(10\;{\mu}g/mouse)$. And then, BRAS (0.2ml/mouse) injected into $CV_4\;and\;BL_{23}$, which are the classical acupuncture points in traditional medicine, for 7 days. And then B and T cells proliferation and cytolytic activity of natural killer (NK) cells were measured. Intraperitoneal injection of glucocorticoid decreased lysozyme activity in macrophage and cytolytic activity of NK cell. B and T cell proliferation were significantly increased in aqua-acupuncture group compared to normal group. On the other hand, BRAS significantly increased the lysozyme activity in macrophage, and the cytolytic activity of purified NK cell on K562. These results suggest that BRAS at $CV_4\;and\;BL_{23}$ may proliferate B and T cells that are suppressed by glucocorticoid and activate NK cell activity.

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Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing's syndrome

  • Kim, Mina;Lee, Hae-Ahm;Cho, Hyun-Min;Kang, Seol-Hee;Lee, Eunjo;Kim, In Kyeom
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.1
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    • pp.23-33
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    • 2018
  • Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

Effects of Noise Stress on Cortisol and Glucocorticoid Receptor Expression of Korean Rockfish, Sebastes schlegeli (소음 스트레스가 조피볼락, Sebastes schlegeli의 cortisol과 glucocorticoid receptor의 발현에 미치는 영향)

  • Shim, Min Kyung;Han, Kyung Nam
    • Korean Journal of Ichthyology
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    • v.20 no.3
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    • pp.149-155
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    • 2008
  • The effects of noise stress response on hematological parameters (hemoglobin, hematocrit and MCHC) and plasma parameters (cortisol, glucose and albumin) in Korean rockfish (Sebastes schlegeli), a very important commercial marine fish in Korea, were investigated. These parameters were analyzed on fish exposed to an explosion of noise. There were no significant differences or trends in hematological parameters (hematocrit; control $29.7{\pm}4.8%$, experiment 32.0 35.5%; hemoglobin; control $6.5{\pm}0.7g/dL$, experiment 6.2 7.8 g/dL; MCHC; control $19.6{\pm}0.6g/dL$, experiment 19.9~22.2 g/dL). However, plasma cortisol and glucose exhibited significant differences from start to finish and displayed the following patterns (cortisol; control $180.7{\pm}35.4ng/mL$, experiment 247.0 444.5 ng/mL; glucose; control $32.5{\pm}6.3mg/dL$, experiment 50.5 109.0 mg/dL). In addition, the glucocorticoid receptor (GR) mRNA expression and basal levels of various tissues (eye, gills, liver, intestine, skin and gonads) were investigated for the first time in this marine fish. When the Korean rockfish was exposed to explosive noise stress, the GR mRNA was expressed more in the gonads than in other tissues tested and was elevated significantly from two and four times in the liver and gills, respectively, after noise exposure.

Kaiso represses the expression of glucocorticoid receptor via a methylation-dependent mechanism and attenuates the anti-apoptotic activity of glucocorticoids in breast cancer cells

  • Zhou, Lin;Zhong, Yan;Yang, Fang-hui;Li, Zi-bo;Zhou, Jiang;Liu, Xie-hong;Li, Min;Hu, Fang
    • BMB Reports
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    • v.49 no.3
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    • pp.167-172
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    • 2016
  • Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely correlated with glucocorticoid receptor (GR) expression in breast carcinomas. Knockdown of Kaiso increased GR expression, while overexpression of Kaiso inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP experiments demonstrated that endogenous Kaiso was associated with the GR promoter sequence in a methylation-dependent manner. Since glucocorticoids inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti-apoptotic effects. We found that overexpression of Kaiso attenuated the anti-apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential therapeutic target in GC-combination chemotherapy in breast cancer.

An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor

  • Kim, Do-Hyoung;Wright, Anthony;Han, Kyou-Hoon
    • BMB Reports
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    • v.50 no.10
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    • pp.522-527
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    • 2017
  • A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity. We carried out heteronuclear multi-dimensional NMR experiments on hGR tau1c in a more physiological aqueous buffer solution and found that it forms three helices that are ~30% pre-populated. Since pre-populated helices in several TADs were shown to be key elements for transcriptional activity, the three pre-formed helices in hGR tau1c delineated in this study should be critical determinants of the transcriptional activity of hGR. The presence of pre-structured helices in hGR tau1c strongly suggests that the existence of pre-structured motifs in target-unbound TADs is a very broad phenomenon.

Noise-induced Stress Response on Cortisol, Glucose, albumin and Glucocorticoid Receptor Expression in the Japanese eel, Anguilla japonica (소음스트레스에 대한 뱀장어의 코티졸, 글루코스, 알부민과 Glucocorticoid Receptor 유전자 발현 연구)

  • Park, Young-Chul;Kang, Yong-Jin;Jeon, Hyoung-Joo;Han, Kyung-Nam;Baek, Jae-Min;Lee, Wan-Ok;Kim, Jin-Hyoung
    • Korean Journal of Environment and Ecology
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    • v.25 no.6
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    • pp.853-860
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    • 2011
  • We measured blood plasma parameters(cortisol, glucose, albumin) and glucocorticoid receptor(GCR) gene expression level of the Japanese eel(Anguilla japonica) exposed to an explosion noise for an hour in order to evaluate the effects of noise stress and to explore the possibility of these parameters as biomarkers on noise stress for one of this valuable aquaculture species. Plasma cortisol and glucose reached high levels with significant differences compared to the control group, whereas albumin showed a low value after 1 h of exposure. In addition, tissue distribution of GCR gene expression was studied by real-time RT-PCR of ten organs(brain, eye, gill, gonad, heart, intestine, kidney, liver, muscle and skin). Liver showed the highest level of expression in the control followed by gill, muscle and intestine. A time-course study revealed induction in liver, gill, muscle and intestine after 30 min or 1 h of noise exposure.

Profiles of Glucocorticoid Receptor mRNA Expression and Physiological Changes in Response to Osmotic and Thermal Stress Conditions in Black Porgy (Acanthopagrus schlegeli) (염분과 수온 스트레스에 따른 감성돔의 glucocorticoid receptor mRNA 발현 특징과 생리적 변화에 관한 연구)

  • An, Kwang-Wook;Shin, Hyun-Suk;Min, Byung-Hwa;Kil, Gyung-Suk;Choi, Cheol-Young
    • Korean Journal of Ichthyology
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    • v.22 no.1
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    • pp.17-24
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    • 2010
  • The present study investigated the expression of glucocorticoid receptor (GR) mRNA as a stress response during salinity changes (35, 10, and 0 psu) and water temperature changes (from $20^{\circ}C$ to $30^{\circ}C$, $1^{\circ}C$/day) in black porgy. We cloned the full-length GR cDNA from the kidney and examined its expression in the gill, kidney, and intestine by quantitative real-time PCR (QPCR) during salinity and water temperature changes. During salinity changes, the levels of GR mRNA in the gill, kidney, and intestine were highest at 0 psu, and the levels of plasma cortisol and glucose were elevated, but triiodothyronine ($T_3$) decreased. Also, during water temperature changes, the levels of GR mRNA in the gill, kidney, and intestine increased at $30^{\circ}C$. Plasma parameters also increased with an increase in water temperature. Therefore, this upregulation of GR mRNA was a good indicator of stress, such as those resulting from changes in salinity and water temperature.

Relievable Effect of Alpinetin on Dexamethasone-Induced Skin Aging (Alpinetin의 Dexamethasone으로 유도한 피부 노화 완화 효과)

  • Nam, Jin-Ju;Kim, Youn Joon;Kang, Seunghyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.2
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    • pp.163-171
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    • 2016
  • Steroid hormone, glucocorticoid (GC) has strong anti-inflammatory effects by binding to glucocorticoid receptor (GR) inhibiting the expression of inflammatory genes. Therefore, agents that activate the GR have been used for the treatment of dermatitis. However, the agents have side effects such as skin barrier dysfunction and dermal atrophy, inducing skin damage as well as skin aging. It has been reported that GC is activated by 11 beta-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) to increase the activity of the GR. This study aimed to identify natural materials that can effectively inhibit dexamethasone. We found that alpinetin isolated from Alpinia katsumadai extract has a significant effect on this. Alpinetin not only inhibited $11{\beta}$-HSD1 expression, but also suppressed the increase of phosphorylated GR and cortisol concentration. Alpinetin also recovered collagen expression in dexamethasone-treated dermal fibroblasts, and the reduction of dermal thickness in dexamethasnone-treated 3D skin model. These results suggest that alpinetin prevents skin aging induced by the increase of $11{\beta}$-HSD1 expression.