Wonchung Lim
Sejong University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Wonchung Lim.
The Journal of Steroid Biochemistry and Molecular Biology | 2003
Young Joo Lee; YoungRan Jin; Wonchung Lim; SangMi Ji; Songho Choi; Siyoul Jang; Seung-Ki Lee
We have examined the possibility that a component of Panax ginseng, ginsenoside-Rh1, acts by binding to steroid hormone receptors such as receptors for estrogen, glucocorticoid, androgen, and retinoic acid. Ginsenoside-Rh1 activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 microM. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rh1 is estrogen receptor dependent. Ginsenoside-Rh1 induction of luciferase activity was dose-dependent in CV-1 cells transiently transfected with estrogen receptor and reporter plasmids. Next, we evaluated the ability of ginsenoside-Rh1 to induce the estrogen-responsive genes in MCF-7 cells. Ginsenoside-Rh1 increased c-fos and pS2 at the mRNA levels at 24h after treatment, although the effects were not as prominent as 17beta-estradiol. Western blot analysis showed that progesterone receptor protein was induced at 24h of treatment of ginsenoside-Rh1. However, ginsenoside-Rh1 failed to activate the glucocorticoid receptor, the androgen receptor, or the retinoic acid receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that ginsenoside-Rh1 acts as a weak phytoestrogen, presumably by binding and activating the estrogen receptor.
Journal of Hypertension | 2007
Young Min Bae; Ae-Ran Kim; Young-Joo Lee; Wonchung Lim; Yun-Hee Noh; Eun-Ju Kim; Junghwan Kim; Tae-Kyung Kim; Sang Woong Park; Bokyung Kim; Sung-Il Cho; Duk-Kyung Kim; Won-Kyung Ho
Objectives In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, altered reactivity of blood vessels to vasoactive agonists is frequently associated with an elevation in blood pressure. Canonical transient receptor potential (TRPC) channels are believed to encode receptor-operated cation channels (ROC), the activation of which is involved in smooth muscle depolarization and vasoconstriction. The aims of the present study were to investigate whether the ROC current is increased in DOCA-hypertensive rats and determine whether aldosterone directly enhances the expression of TRPC. Methods The nystatin-perforated patch-clamp technique was used for the recording of receptor-stimulated ion currents in mesenteric arterial smooth muscle cells, which were enzymatically dispersed from sham-operated and DOCA-salt hypertensive rats. Expressions of TRPCs were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Western blot analysis. Results Receptor-stimulated currents activated by 5-hydroxytryptamine (serotonin) and norepinephrine were increased significantly in the mesenteric arterial smooth muscle cells of DOCA-salt hypertensive rats compared to sham-operated rats. Ion-substitution experiments revealed that the enhanced currents were cation currents (ROC currents). Enhanced expression of TRPC6 in mesenteric arteries from DOCA-salt hypertensive rats was demonstrated by real-time RT-PCR. Up-regulation of TRPC6 by aldosterone treatment in vitro was also observed in A7r5 cells by RT-PCR and in western blots. Conclusion These results suggest that aldosterone enhances TRPC6 expression and ROC currents in vascular smooth muscle cells, and that this may in turn contribute to altered vascular reactivity and to hypertension.
Breast Cancer Research | 2011
Wonchung Lim; Yeomyung Park; Jungyoon Cho; Choa Park; Joonwoo Park; Young-Kwon Park; Hyunsung Park; Young Joo Lee
IntroductionEstrogen receptor (ER) β is predicted to play an important role in prevention of breast cancer development and metastasis. We have shown previously that ERβ inhibits hypoxia inducible factor (HIF)-1α mediated transcription, but the mechanism by which ERβ works to exert this effect is not understood.MethodsVascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assays. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting, immunoprecipitation, luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to ascertain the implication of ERβ on HIF-1 function.ResultsIn this study, we found that the inhibition of HIF-1 activity by ERβ expression was correlated with ERβs ability to degrade aryl hydrocarbon receptor nuclear translocator (ARNT) via ubiquitination processes leading to the reduction of active HIF-1α/ARNT complexes. HIF-1 repression by ERβ was rescued by overexpression of ARNT as examined by hypoxia-responsive element (HRE)-driven luciferase assays. We show further that ERβ attenuated the hypoxic induction of VEGF mRNA by directly decreasing HIF-1α binding to the VEGF gene promoter.ConclusionsThese results show that ERβ suppresses HIF-1α-mediated transcription via ARNT down-regulation, which may account for the tumour suppressive function of ERβ.
British Journal of Pharmacology | 2014
Wonchung Lim; Choa Park; Myeong Kuk Shim; Yong Hee Lee; You Mie Lee; Young Joo Lee
The COX‐2/PGE2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumourigenesis. However, the mechanism by which glucocorticoid receptors (GRs) inhibit COX‐2 during hypoxia has not been elucidated. Hence, we explored the mechanisms underlying glucocorticoid‐mediated inhibition of hypoxia‐induced COX‐2 in human distal lung epithelial A549 cells.
FEBS Letters | 2009
Wonchung Lim; Jungyoon Cho; Hyeok-Yi Kwon; Yeomyeong Park; Mee-Ra Rhyu; Young Joo Lee
Previously, we showed that hypoxia induces ligand‐independent estrogen receptor (ER)α activation. In this study, we found that hypoxia activated the ERβ‐mediated transcriptional response in HEK293 cells in the absence of estrogen. ERβ transactivation was induced by the expression of the hypoxia‐inducible factor 1α (HIF‐1α) under normoxia. ERβ interacted with HIF‐1α, and SRC1 and CBP potentiated the effect of HIF‐1α on ERβ‐mediated transcription. We then examined the effect of ERβ on HIF1‐α transactivation. Surprisingly, ERβ attenuated the transcriptional activity of HIF‐1α, as measured by HRE‐driven reporter gene expression and hypoxic induction of VEGF mRNA in HEK293 cells. Taken together, these data show that HIF‐1α activates ERβ‐mediated transcription in the absence of a ligand, and ERβ inhibits HIF‐1α‐mediated transcription.
Biochemical and Biophysical Research Communications | 2015
Wonchung Lim; Joonwoo Park; Yong Hee Lee; Jiyong Hong; Young Joo Lee
Subglutinol A is an immunosuppressive α-pyrone diterpenoid isolated from Fusarium subglutinans that exhibits osteogenic activity. Several non-steroid mycotoxins isolated from various strains of Fusarium fungi exhibit female steroid hormone activities. In this study, we characterized the estrogenic activity of subglutinol A (1). Subglutinol A blocked the 17β-estradiol-induced activation of reporter plasmids and endogenous estrogen-responsive target genes in a dose-dependent manner and efficiently destabilized ER proteins as shown using the estrogen receptor antagonist ICI 182,780. Subglutinol A also displaced the specific binding of [(3)H]17β-estradiol from ER in MCF-7 whole-cell ligand binding assays. These data demonstrate the potential of subglutinol A as an ER antagonist though its competition with 17β-estradiol for direct ER association.
Phytomedicine | 2015
Wonchung Lim; Myeong Kuk Shim; Sikwan Kim; Young Joo Lee
BACKGROUND Korean red ginseng (KRG) is a traditional herbal medicine made by steaming and drying the fresh ginseng, leading to chemical transformation of some components by heat. It ameliorates various inflammatory diseases and strengthens the endocrine, immune, and central nervous systems. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumorigenesis. PURPOSE In this study we examined the effects and the mechanism underlying Korean red ginseng water extract (KRG-WE) inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells. STUDY DESIGN The effect of the KRG on suppression of hypoxia-induced COX-2 in A549 cells were determined by Western blot and/or qRT-PCR. The anti-invasive effect of KRG-WE was evaluated on A549 cells using matrigel invasion assay. The activation of glucocorticoid receptor (GR) and sirtuin1 (Sirt1) was examined by using specific inhibitors. RESULTS We first observed that hypoxia induced COX-2 protein and mRNA levels and promoter activity were suppressed by KRG-WE. Second, we observed that hypoxia-induced cell migration is dramatically reduced by KRG-WE. Third, we found that the effect of KRG-WE was not antagonized by the GR antagonist RU486 implying that the effect is mediated other than GR pathway. Finally, we demonstrated that inhibition of Sirt1 abolished the effect of KRG-WE on hypoxia-induced COX-2 suppression and cell-invasion indicating that the suppression is mediated by Sirt1. CONCLUSION Taken together, KRG-WE inhibits the hypoxic induction of COX-2 expression and cell invasion through Sirt1 activation. Our results imply that KRG-WE could be effective for suppression of inflammation under hypoxia.
Journal of Molecular Medicine | 2011
Yeomyung Park; Joonwoo Park; Yong Hee Lee; Wonchung Lim; Byung-Chul Oh; Chan-Young Shin; Wansup Kim; Young Joo Lee
Mammalian MST2 kinase plays an important role in cell proliferation, survival, and apoptosis. In search of interacting proteins of MST2, we found that estrogen receptor α (ERα) co-immunoprecipitates with MST2 and its adaptor protein human Salvador (hSAV). Using reporter assays, we observed that overexpression of MST2 and hSAV leads to ligand-independent activation of ERα in human breast cancer MCF-7 cells, which was attenuated by the knockdown of hSAV. Furthermore, using truncated mutants of hSAV, we observed that the C terminus of hSAV is necessary and sufficient for the induction of ERα transactivation. The expression of hSAV and MST2 results in the phosphorylation of ERα at serine residues 118 and 167 and represses ERα expression. We then investigated the incidence of MST2 and ERα expression with other tumor biomarkers using commercially available tissue microarrays. Among 40 breast cancer samples analyzed, 60% (24 out of 40) expressed MST2. Nineteen among the 40 cases were MST2-positive and ERα-negative, implying a correlation between expressions of MST2 with loss of ERα in breast tumor samples. This study suggests that MST and hSAV act as novel co-regulators of ERα and may play an important role in breast cancer pathogenesis.
Cancer Research | 2015
Wonchung Lim; Young Joo Lee
The COX-2/PGE2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumourigenesis. Glucocorticoid receptor (GR) strongly suppresses COX-2 expression induced by inflammatory stimuli. However, the role of GR pathway on COX-2 induction by hypoxia and the mechanisms involved are not known. We examined whether the hypoxia induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Overexpression of glucocorticoid-induced leucine zipper (GILZ) inhibited hypoxia-induced COX-2 promoter activity, and knockdown of GILZ by shRNA reduced glucocorticoid inhibition of hypoxia-induced COX-2 expression. Finally, we show that dexamethasone and GILZ inhibits cell invasion by hypoxia in A549 cells. Our results suggest that GR inhibits the hypoxic induction of COX-2 expression via GILZ and regulates cell invasion under hypoxia in A549 cells. Citation Format: WonChung Lim, YoungJoo Lee. GILZ mediates glucocorticoid action and inhibits hypoxia-induced COX-2 expression in A549 cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B29. doi:10.1158/1538-7445.CHTME14-B29
Planta Medica | 2006
Wankyu Park; Wonchung Lim; Jungyoon Cho; Hiroyasu Inoue; Mee-Ra Rhyu; Young-Joo Lee