• Title/Summary/Keyword: RETINOIC ACID

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Ethacrynic Acid and Citral Suppressed the All Trans Retinoid-Induced Monocyte Chemoattractant Protein-1 Production in Human Dermal Fibroblasts

  • Kim, Kwang-Mi;Noh, Min-Soo;Kim, Soo-Hyun;Park, Mi-Kyung;Lee, Hye-Ja;Kim, Soo-Youl;Lee, Chang-Hoon
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.71-76
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    • 2010
  • Skin irritation caused by retinol and retinoic acid results in mild erythema called as retinoid dermatitis. To develop compounds modulating the retinoid dermatitis, we tried to establish the screening method for retinoid dermatitis. At first we examined the inflammatory cytokine profile in neonatal human dermal fibroblasts which are known to be one of main site of retinoid action. As a result, interleukin-8 (IL-8) and monocytes chemoattractant protein-1 (MCP-1) were significantly produced by all trans retinoic acid (ATRA) and all trans retinol (ATROL) in dermal fibroblasts. Especially the production of MCP-1 was more than that of IL-8. The production of MCP-1 by retinoid was dose-dependently increased, continuing up to 24 hrs. After then using ethacrynic acid (ECA) known to reduce mouse ear edema induced by ATRA, we checked whether ECA suppressed the production of MCP-1. As a result, ECA effectively suppressed the production of MCP-1 in the ATRA- or ATROL-treated-fibroblasts. These results suggested that screening method effectively reflects the in vivo anti-inflammatory activity of ECA. It was reported that citral inhibited the enzyme involved in the conversion of ATROL to ATRA. We showed that citral suppressed the production of MCP-1 in ATROL-treated fibroblasts. We expect these finding might be helpful to find useful compounds modulating the side effects of retinoid or retinoid dermatitis.

Improvement of Motor Behavior of Parkinson's Disease Animal Model by Nurr1 Transfected Human Embryonic Stem Cells

  • Lee, Chang-Hyun;Cho, Hwang-Yun;Kim, Yong-Sik;Kim, Eun-Young;Lee, Won-Don;Park, Sepill;Lim, Jin-Ho
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.274-274
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    • 2004
  • The purpose of this study is to evaluate the efficacy of in vitro differentiated human embryonic stem (MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models. MB03 cell was genetically modified to express Nurr1 protein (Nr#24/MB03) and was induced to differentiate according to 2- /4+ protocol using retinoic acid and ascorbic acid. (omitted)

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Effect of retinoic acid on the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase (Herpes Simplex Virus thymidine kinase gene을 이용한 유전자 치료에서 retinoic acid가 bystander effect에 미치는 영향)

  • Park, Jae Yong;Kim, Chang Ho;Jung, Tae Hoon;Albelda, Steven M.
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.1
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    • pp.162-174
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    • 1997
  • Background : Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase/ganciclovir (HSVtk) "prodrug" system. Since retinoids have been reported to increase GJIC by induction of connexin 43 expression, we hyporthesized that treatment of tumor cells with retinoic acid could augment the bystander effect of the HSVtk/GCV system and result in improved tumor cell killing by enhancing GJIC. Methods : We transferred HSVtk gene to SKHep-J cell line that does not express connexin43, and also transferred the gene to human and murine mesothelioma cell lines that express connexin43. We verified that retinoic acid enhanced GJIC utilizing a functional double-dye transfer study and evaluated the effects of retinoic acid on the growth rate of tumor cells. We then tested the effects of retinoic acid on bystander-mediated cell killing. Results : Addition of all-trans retinoic acid (RA) increased GJIC in cell lines expressing connexin 43 and was asspciated with more efficient in vitro bystander killing in cells transduced with HSVtk via adenoviral and retroviral vectors. In contrast, there was no increase in the efficiency of the bystander effect after exposure to RA in a cell line which had no delectable connexin 43. Conclusion : These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effect and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk system to treat tumors.

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A Novel All-trans Retinoid Acid Derivative Induces Apoptosis in MDA-MB-231 Breast Cancer Cells

  • Wang, Bei;Yan, Yun-Wen;Zhou, Qing;Gui, Shu-Yu;Chen, Fei-Hu;Wang, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10819-10824
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    • 2015
  • Aims: To explore the effect and probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethylphenyl ester (ATPR) on apoptosis of MDA-MB-231 breast cancer cells. Materials and Methods: MTT assays were performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. Morphologic changes were observed by microscopy. The apoptosis rates and cell cycling of MDA-MB-231 cells treated with ATRA or ATPR were assessed using flow cytometry analysis. Expression of retinoic acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by Western blotting. Results: Treatment of the cells with the addition of $15{\mu}mol/L$ ATPR for 48 h clearly demonstrated reduced cell numbers and deformed cells, whereas no changes in the number and morphology were observed after treatment with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were treated by ATPR ($15{\mu}mol/L$) whereas ATRA ($15{\mu}mol/L$) had no apoptotic effect. ATPR inhibited the phosphorylation of ERK, JNK, and p38 while ATRA had no significant effect. ATPR inhibited the expression of BiP and increased the expression of Chop at the protein level compared with control groups, ATRA and ATPR both decreased the protein expression of $RXR{\alpha}$, ATPR reduced the protein expression of $RAR{\beta}$ and $RXR{\beta}$ while ATRA did not decrease $RAR{\beta}$ or $RXR{\beta}$. Conclusions: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells, possible mechanisms being binding to $RAR{\beta}/RXR{\beta}$ heterodimers, then activation of ER stress involving the MAPK pathway.

Retinoic acid가 계배 Wingbud의 조직발생에 미치는 영향

  • 한만종;김원선
    • Environmental Mutagens and Carcinogens
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    • v.10 no.1
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    • pp.11-24
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    • 1990
  • 발생중인 계배의 날개에서 지골의 복제를 유발하는 retinoic acid(RA)가 날개의 조직발생에 미치는 영향을 알아보았다. Hamburger와 Hamilton stage 19에 도달한 계배의 wingbud 앞부분에 RA를 처리하고 처리후 24, 48, 72시간이 경과되었을 때 나타난 조직상의 변화를 조사하여 다음과 같은 결과를 얻었다. (1) RA처리는 처리부위와 인접한 조직에서 세포밀도의 감소를 초래하였으며 처리부위와 떨어진 부위에서는 오히려 세포밀도의 증가를 유발하였다. (2)RA처리는 apical ectodermal ridge(AER) 길이의 신장을 유발하였고 또한 그 위치의 전단부 쪽으로의 이동을 가져왔다. (3) 이러한 조직상의 변화는 처리후 24시간에 나타나 72시간까지 계속 되었으며, 특히 처리후 72시간에는 날개의 앞부분에서 원래의 AER외에 복제된 AER을 관찰할 수 있었다. 이러한 RA처리에 다른 조직상에서의 변화는 RA처리에 의하여 유발되는 지골복제현상이 처리후 24시간내에 시작되는 중배엽성조직 및 중배엽조직의 성장과 분화에 필수적인 AER의 변화에 기인함을 시사하고 있다.

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