• Title/Summary/Keyword: RETINOIC ACID

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Thyroid Hormones Receptor/Reporter Gene Transcription Assay for Food Additives and Contaminants

  • Jeong Sang-Hee;Cho Joon-Hyoung
    • Toxicological Research
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    • v.21 no.4
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    • pp.333-338
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    • 2005
  • Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.

Zebrafish (Danio rerio) Thyroid Hormone Receptor $\alpha$1 Counteracts Retinoic Acid-induced Transcription

  • Rhee, Myubg-Chull;Lee, Woonghee;Chang, Mi-Sook;Lee, Sang-Kyou
    • Animal cells and systems
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    • v.2 no.1
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    • pp.133-137
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    • 1998
  • The present study aims to characterize a cDNA encoding zebrafish thyroid hormone receptor $\alpha{1}$ $(zTR\alpha{1)}$ in order to investigate its possible role in the early stage of embryonic development. A mobility shift assay showed that $zTR\alpha{1}$ overexpressed in COS7 cells specifically bound to thyroid hormone response element (TRE). In addition, the specific interaction of anti-rat $TR\alpha{1}$ antibodies with $zTR\alpha1$/TRE complexes demonstrated that the cDNA clone encoded zebrafish thyroid hormone receptor $\alpha{1}$. Transient cotransfection assays showed that $zTR\alpha{1}$ repressed the transcription which was induced by retinoic acid (RA), a well-characterized embryonic morphogen. These results suggest that zTRal may be involved in regulating the RA-induced gene transcription during early embryonic development.

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Morphogenetic and neuronal characterization of human neuroblastoma multicellular spheroids cultured under undifferentiated and all-trans-retinoic acid-differentiated conditions

  • Jung, Gwon-Soo;Lee, Kyeong-Min;Park, Jin-Kyu;Choi, Seong-Kyoon;Jeon, Won Bae
    • BMB Reports
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    • v.46 no.5
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    • pp.276-281
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    • 2013
  • In this study, we aimed to compare the morphogenetic and neuronal characteristics between monolayer cells and spheroids. For this purpose, we established spheroid formation by growing SH-SY5Y cells on the hydrophobic surfaces of thermally-collapsed elastin-like polypeptide. After 4 days of culture, the relative proliferation of the cells within spheroids was approximately 92% of the values for monolayer cultures. As measured by quantitative assays for mRNA and protein expressions, the production of synaptophysin and neuronspecific enolase (NSE) as well as the contents of cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins are much higher in spheroids than in monolayer cells. Under the all-trans-retinoic acid (RA)-induced differentiation condition, spheroids extended neurites and further up-regulated the expression of synaptophysin, NSE, CAMs, and ECM proteins. Our data indicate that RA-differentiated SH-SY5Y neurospheroids are functionally matured neuronal architectures.

The Effects of Fetal Bovine Serum, Epidermal Growth Factor, and Retinoic Acid on Adult Rat Islets Embedded in Collagen Gels

  • Shin, Jun-Seop;Chang, Hyo-Ihl;Sung, Ha-Chin;Kim, Chan-Wha
    • Journal of Microbiology and Biotechnology
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    • v.9 no.2
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    • pp.150-156
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    • 1999
  • The induction of proliferation of adult rat islets was investigated under various culture conditions. The islets were isolated from male Sprague-Dawley rats and subsequently embedded in collagen gels, which mimic the in vivo three-dimensional surroundings. During the culture period, the effects of heterologous serum (fetal bovine serum, FBS), epidermal growth factor (EGF), and retinoic acid (RA) on islet growth were examined with respect to the morphological and total DNA content changes. To investigate these changes at the cellular level, whole mount immunocytochemistry using specific antibodies for insulin and glucagon was performed. The results showed that (i) collagen gels as an extracellular matrix can maintain islets in a similar way to that in vivo, (ii) heterologous serum (FBS) had stimulatory effects on islet proliferation in a dose-dependent manner, (iii) RA had inhibitory effects on islet proliferation induced by the serum in a dose-dependent manner, (iv) EGF had weak inhibitory effects on islet proliferation induced by the serum except at the concentration of 10 nM where its effect was not significant, and (v) whole mount immunocytochemistry revealed that newly proliferated islet cells were mainly $\beta$-and $\alpha$-cells.

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Recent Progress in Orphan Nuclear Hormone Receptors

  • Lee, Yoon-Kwang;Tzameli, Iphigeoia;Zavacki, Ann Marie;Moore, David D.
    • BMB Reports
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    • v.31 no.5
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    • pp.419-426
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    • 1998
  • The nuclear hormone receptor superfamily currently includes approximately equal numbers of conventional receptors and orphan receptors, which do not have known ligands. Here, we review recent progress from this laboratory on three orphans, two of which are moving from orphan to conventional receptor status. Perhaps the most unusual is CAR, which is a constitutive transactivator in the absence of ligands but becomes transcriptionally inactive in the presence of its ligands, which are androgen metabolites. The response of CAR to its ligands is thus opposite to that of the conventional receptor paradigm. RIP14 (also known as FXR) is activated by both all-trans retinoic acid and a synthetic retinoid previously thought to specifically target the retinoic acid receptors (RARs), and thus appears to be a novel retinoid receptor. Finally, SHP is a novel orphan that lacks a DNA binding domain and interacts with a number of other receptor superfamily members. While it generally inhibits its targets, including CAR, the retinoid X receptor (RXR), and the estrogen receptor (ER), it stimulates transactivation by the orphan SF-1.

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Innate immune recognition of respiratory syncytial virus infection

  • Kim, Tae Hoon;Lee, Heung Kyu
    • BMB Reports
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    • v.47 no.4
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    • pp.184-191
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    • 2014
  • Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in infants and young children. Severe clinical manifestation of RSV infection is a bronchiolitis, which is common in infants under six months of age. Recently, RSV has been recognized as an important cause of respiratory infection in older populations with cardiovascular morbidity or immunocompromised patients. However, neither a vaccine nor an effective antiviral therapy is currently available. Moreover, the interaction between the host immune system and the RSV pathogen during an infection is not well understood. The innate immune system recognizes RSV through multiple mechanisms. The first innate immune RSV detectors are the pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-biding oligomerization domain (NOD)-like receptors (NLRs). The following is a review of studies associated with various PRRs that are responsible for RSV virion recognition and subsequent induction of the antiviral immune response during RSV infection.

Anti-wrinkle effect of bone morphogenetic protein receptor 1a-extracellular domain (BMPR1a-ECD)

  • Yoon, Byung-Hak;Jeon, Yun-Hui;Hwang, Byunghee;Kwon, Hyuknam;Choe, Senyon;Yang, Zungyoon
    • BMB Reports
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    • v.46 no.9
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    • pp.465-470
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    • 2013
  • Bone morphogenetic proteins (BMPs) have diverse and important roles in the proliferation and differentiation of adult stem cells in our tissues. Especially, BMPs are well known to be the main inducers of bone formation, by facilitating both proliferation and differentiation of bone stem cells. Interestingly, in skin stem cells, BMPs repress their proliferation but are indispensable for the proper differentiation into several lineages of skin cells. Here, we tested whether BMP antagonists have an effect on the prevention of wrinkle formation. For this study we used an in vivo wrinkle-induced mouse model. As a positive control, retinoic acid, one of the top anti-wrinkle effectors, showed a 44% improvement compared to the non-treated control. Surprisingly, bone morphogenetic protein receptor 1a extracellular domain (BMPR1a-ECD) exhibited an anti-wrinkle effect which was 6-fold greater than that of retinoic acid. Our results indicate that BMP antagonists will be good targets for skin or hair diseases.

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

  • Wang, Xue-Jian;Duan, Yu;Li, Zong-Tao;Feng, Jin-Hong;Pan, Xiang-Po;Zhang, Xiu-Rong;Shi, Li-Hong;Zhang, Tao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6343-6347
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    • 2014
  • Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.