• Title/Summary/Keyword: Retinoic acid receptor antagonist

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All-trans retinoic acid alters the expression of adipogenic genes during the differentiation of bovine intramuscular and subcutaneous adipocytes

  • Chung, Ki Yong;Kim, Jongkyoo;Johnson, Bradley J.
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1397-1410
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    • 2021
  • The present study was designed to determine the influence of all-trans retinoic acid (ATRA) on adipogenesis-related gene regulation in bovine intramuscular (IM) and subcutaneous (SC) adipose cells during differentiation. Bovine IM and SC adipocytes were isolated from three 19-mo-old, crossbred steers. Adipogenic differentiation was induced upon cultured IM and SC preadipocytes with various doses (0, 0.001, 0.01, 0.1, 1 µM) of ATRA. After 96 h of incubation, cells were harvested and used to measure the gene expression of CCAAT/Enhancer binding protein β (C/EBPβ), peroxisome proliferator-activated receptor (PPAR) γ, glucose transporter 4 (GLUT4), stearoyl CoA desaturase (SCD), and Smad transcription factor 3 (Smad3) relative to the quantity of ribosomal protein subunit 9 (RPS 9). Retinoic acid receptor (RAR) antagonist also tested to identify the effect of ATRA on PPARγ -RAR related gene expression in IM cells. The addition of ATRA to bovine IM decreased (p < 0.05) expression of PPARγ. The expression of PPARγ was also tended to be downregulated (p < 0.1) in high levels (10 µM) of ATRA treatment in SC cells. The treatment of RAR antagonist increased the expression of PPARγ in IM cells. Expression of C/EBPβ decreased (p < 0.05) in SC, but no change was observed in IM (p > 0.05). Increasing levels of ATRA may block adipogenic differentiation via transcriptional regulation of PPARγ. The efficacy of ATRA treatment in adipose cells may vary depending on the location.

Estrogen, Androgen, and Retinoic Acid Hormone Activity of Ginseng Total Saponin (인삼 총 사포닌의 에스트로젠, 안드로젠, 레티노익산 호르몬 수용체에 대한 활성)

  • Ji, Sang-Mi;Lee, Young-Joo
    • Journal of Ginseng Research
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    • v.27 no.3
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    • pp.93-97
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    • 2003
  • Alternative or complementary medicine plays an important role in health care system. Ginseng, being one of the most popular oriental herbs, is believed to contain various steroid hormone activity. Ginseng has been demonstrated pharmacological effect in the cardiovascular, endocrine, central nervous, and immune system. Our objective was to study that total saponin might mediate some of their actions by binding to the steroid hormone receptor, as they share many of the actions of steroid hormone in various physiological system. Using total saponin from Panax Ginseng, we have studied the possibility of total saponin being a potential estrogen receptor, androgen receptor, and retinoic acid receptor ligand. Total saponin activated the transcription of both the estrogen and androgen responsive luciferase reporter plasmids at a concentration of 100$\mu\textrm{g}$/ml in COS cells transiently transfected with the corresponding receptor and hormone responsive receptor plasmids. And total saponin caused a concentration-dependent stimulation of estrogen receptor. Total saponin increased the expression of estrogen responsive c-fos proto-oncogene at the protein level in MCF7 cells at 24 h treatment as examined by Western analysis. The c-fos induction was used as a specific marker of estrogen responsiveness. This activation was inhibited by the specific estrogen receptor antagonist, ICI 182,780. However, total saponin failed to activate the retinoic acid receptor in COS cells transiently transfected with the corresponding receptor and retinoic acid responsive reporter plasmids. These results show that total saponin is capable of activating estrogen and androgen receptors.

IL-1 Receptor Antagonist Reduced Chemical-Induced Keratinocyte Apoptosis through Antagonism to IL-1α/IL-1β

  • Lee, Hyejin;Cheong, Kyung Ah;Kim, Ji-Young;Kim, Nan-Hyung;Noh, Minsoo;Lee, Ai-Young
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.417-423
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    • 2018
  • Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.

$Ginsenoside-R_{b1}$ Acts as a Weak Phytoestrogen in MCF-7 Human Breast Cancer Cells

  • Lee, Young-Joo;Jin, Young-Ran;Lim, Won-Chung;Park, Wan-Kyu;Cho, Jung-Yoon;Jang, Si-Youl;Lee, Seung-Ki
    • Archives of Pharmacal Research
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    • v.26 no.1
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    • pp.58-63
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    • 2003
  • Ginseng has been recommended to alleviate the menopausal symptoms, which indicates that components of ginseng very likely contain estrogenic activity. We have examined the possibility that a component of Panax ginseng, $ginsenoside-R_{b1}$ acts by binding to estrogen receptor. We have investigated the estrogenic activity of $ginsenoside-R_{b1}$ in a transient transfection system using estrogen-responsive luciferase plasmids in MCF-7 cells. $ginsenoside-R_{b1}$ activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 $\mu$M. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of $ginsenoside-R_{b1}$ is estrogen receptor dependent. Next, we evaluated the ability of $ginsenoside-R_{b1}$ to induce the estrogen-responsive gene c-fos by semi-quantitative RT-PCR assays and Western analyses. $ginsenoside-R_{b1}$ increased c-fos both at mRNA and protein levels. However, $ginsenoside-R_{b1}$ failed to activate the glucocorticoid receptor, the retinoic acid receptor, or the androgen receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that $ginsenoside-R_{b1}$ acts a weak phytoestrogen, presumably by binding and activating the estrogen receptor.