• Title/Summary/Keyword: Retinoic Acid

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Photodynamically induced endothelial cell injury and neutrophil-like HL-60 adhesion

  • Takahashi, Miho;Nagao, Tomokazu;Matsuzaki, Kazuki;Nishimura, Toshihiko;Minamitani, Haruyuki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.518-520
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    • 2002
  • Photodynamic therapy (PDT) is a treatment modality based on photochemical reaction and the resultant cytotoxic reactive oxygen species. The platelet thrombus formation leading to stasis observed in vivo during PDT is called vascular shut down (VSD) effect. To investigate the mechanism of the VSD effect, we observed Human Umblical Vein Endothelial Cell (HUVEC) injury induced by photochemical reaction. We observed cell retraction and blebbing after PDT. It seems that the injury was not fetal and only morphological change. Then, the cytoplasm was stained by Calcein-AM and subendothelial area was evaluated from fluorescence microscopy. The rate of subendothelial area after PDT increased significantly. Second, we investigated interaction between neutrophils and HUVEC. Human promyelocytic leukemia cells (HL-60) were differentiated into neutrophil by incubation with all-trans retinoic acid. Calcein-AM labeled neutrophil adhesion to HUVEC was evaluated from fluorescence microscopy. PDT-induced neutrophil adhesion to HUVEC depended more on the exposure of subendothlial area than on neutrophil activation. This result suggests that there is a certain interaction between neutrophil and HUVEC during PDT.

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Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation

  • Lee, Na-Rae;Kim, Hye-In;Choi, Myung-Soo;Yi, Chae-Min;Inn, Kyung-Soo
    • Molecules and Cells
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    • v.38 no.9
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    • pp.759-764
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    • 2015
  • Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF-${\kappa}B$ and interferon production. TRIM25 is required for the full activation of NF-${\kappa}B$ at the downstream of MAVS, while it is not involved in IRF3 nuclear translocation. Mechanical studies showed that TRIM25 is involved in TRAF6-mediated NF-${\kappa}B$ activation. These collectively indicate that TRIM25 plays an additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via activation of NF-${\kappa}B$.

miRNA-222 Modulates Differentiation of Mouse Embryonic Stem Cells

  • Ahn, Hee-Jin;Jung, Jee-Eun;Park, Kyung-Soon
    • Development and Reproduction
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    • v.15 no.4
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    • pp.331-338
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    • 2011
  • MicroRNAs (miRNAs) function as a key regulator of diverse cellular functions. To find out novel miRNAs that promote the differentiation of mouse embryonic stem cells (mESCs), we compared the miRNAs expression profiles of mESCs under self-renewal vs. differentiation states. We noticed that miR-222 was highly expressed during the differentiation of mESCs. Quantitative RT-PCR analysis revealed that expression of miR-222 was up-regulated during the embryonic bodies formation and retinoic acid -dependent differentiation. When miR-222 was suppressed by antogomiR-222, the differentiation of mESCs was delayed compared to control. Self-renewal marker expression or cell proliferation was not affected but the expression of lineage specific marker was suppressed by the treatment of miR-222 inhibitor during the differentiation of mESCs. Taken together, these results suggest that miR-222 functions to promote the differentiation of mESCs by regulating expression of differentiation related genes.

Pattern-Recognition Receptor Signaling Initiated From Extracellular, Membrane, and Cytoplasmic Space

  • Lee, Myeong Sup;Kim, Young-Joon
    • Molecules and Cells
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    • v.23 no.1
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    • pp.1-10
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    • 2007
  • Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.

Preparation and Evaluation of Cubic Liquid Crystalline Phase Gel and Cubosome containing Polyethoxylated Retinamide (폴리에톡시레이티드레틴아마이드를 함유한 입방상 액정 젤 및 큐보좀의 제조 및 평가)

  • Kyong, Kee-Yeol;Jee, Ung-Kil;Cho, Wan-Goo
    • Journal of Pharmaceutical Investigation
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    • v.37 no.2
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    • pp.85-94
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    • 2007
  • The objective of this study is to prepare a stable delivery systems containing polyethoxylated retinamide(PERA) - derivatives of retinoic acid, effective anti-wrinkle and anti-acne agent. Cubic liquid crystalline phase gel (CLCPG) and cubosomes containing various concentrations of PERA were prepared to investigate the physicochemical properties. Furthermore, stability and transdermal absorption efficacy of the CLCPG containing PERA were investigated in comparison with oil-in-water (O/W) emulsions which are predominantly used as a topical formulation. CLCPG increase the stability of PERA in comparison with O/W emulsion. For tropical application, CLCPG containing PERA shows higher moisturizing effect than that of O/W emulsion. In skin permeation test, CLCPG shows higher PERA deposit on epidermis. With its specific physicochemical property caused by the glyceryl oleate, CLCPG itself could be used for stabilizer of various actives and applied as an effective delivery system for topical application. Cubosome, nano-sized dispersed CLCPG, is also expected to be applied in a various field of industry like food, cosmetics and pharmaceuticals.

Alleviative Effects of Jujube Water Extract on the Inflammation and Barrier Damage in Hairless Mice Skin (Hairless 마우스에서 대추 열수추출물의 피부내 염증 및 장벽 손상 완화 효과)

  • Choi, So-Young;Kim, Young-Chul
    • Environmental Analysis Health and Toxicology
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    • v.24 no.4
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    • pp.351-357
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    • 2009
  • To investigate the alleviative effects of jujube water extract (JWE) on the inflammation and skin barrier damage, both the irradiation of UVB and the application of squalene monohydroperoxide (Sq-OOH) were applied to the back skin of experimental animals for 4 weeks. And at the same time experimental materials were applied topically. Six weeks female SKH-1 hairless mice were divided into five groups (five animals for each group) including normal (N; saline), control (C; UVB+Sq-OOH+saline), vehicle control (VC; UVB+Sq-OOH+vehicle), positive control (PC; UVB+Sq-OOH+0.01% retinoic acid) and experimental (E; UVB+Sq-OOH+JWE) groups. The skin erythema index in the E group was significantly low compared to the C group (p<0.05). Lipid (p<0.05) and water (p<0.01) capacities in the E group were significantly high compared to the C group. In comparison with the C group, E group showed a relatively well preserved lipid lamellae in the epidermis and a relatively much less infiltration of mast cells in the dermis or hypodermis. As for the both absolute and relative weights of the spleen, PC group were significantly higher than the other groups. These results suggest that JWE have a considerably inhibitory effect on the inflammation and the skin barrier damage induced by UVB irradiation and Sq-OOH application.

Cyclic AMP response element binding (CREB) protein acts as a positive regulator of SOX3 gene expression in NT2/D1 cells

  • Kovacevic-Grujicic, Natasa;Mojsin, Marija;Popovic, Jelena;Petrovic, Isidora;Topalovic, Vladanka;Stevanovic, Milena
    • BMB Reports
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    • v.47 no.4
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    • pp.197-202
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    • 2014
  • SOX3 is one of the earliest neural markers in vertebrates, playing the role in specifying neuronal fate. In this study we have established first functional link between CREB and human SOX3 gene which both have important roles in the nervous system throughout development and in the adulthood. Here we demonstrate both in vitro and in vivo that CREB binds to CRE half-site located -195 to -191 within the human SOX3 promoter. Overexpression studies with CREB or its dominant-negative inhibitor A-CREB indicate that this transcription factor acts as a positive regulator of basal SOX3 gene expression in NT2/D1 cells. This is further confirmed by mutational analysis where mutation of CREB binding site results in reduction of SOX3 promoter activity. Our results point at CREB as a positive regulator of SOX3 gene transcription in NT2/D1 cells, while its contribution to RA induction of SOX3 promoter is not prominent.

DIFFERENTIATION MECHANISM OF GINSENOSIDES IN CULTURED MURINE F9 TERATOCARCINOMA STEM CELLS

  • Lee H.Y.;Kim S.I.;Lee S.K.;Chung H.Y.;Kim K.W.
    • Proceedings of the Ginseng society Conference
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    • 1993.09a
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    • pp.127-131
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    • 1993
  • The effects of total ginseng saponin. extracts of Panax ginseng C.A. Meyer, on the differentiation of F9 teratocarcinoma stem cells were studied. F9 stem cells cultured in the presence of ginseng saponin together with dibutyric cAMP became parietal endoderm - like cells. Moreover, the expressions of differentiation marker genes. laminin. type IV collagen. and retinoic acid $receptor-{\beta}(RAR{\beta})$ were increased after treatment of ginseng saponin. Among various ginsenosides purified from crude ginseng saponin, $Rh_1\;and\;Rh_2$ caused the differentiation of F9 cells most effectively. Since ginsenosides and steroid hormone show resemblance in chemical structure. we studied the possibility of the involvement of a steroid receptor in the differentiation process induced by ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarding as a steroid receptor was detected in F9 cells cultured in the medium containing ginseng saponin. Based on these data, we suggest that ginseng saponin, especially ginsenosides $Rh_1\;and\;Rh_2$ cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a steroid receptor or its analogous nuclear receptor.

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Upregulation of NF-κB upon differentiation of mouse embryonic stem cells

  • Kim, Young-Eun;Kang, Ho-Bum;Park, Jeong-A;Nam, Ki-Hoan;Kwon, Hyung-Joo;Lee, Young-Hee
    • BMB Reports
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    • v.41 no.10
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    • pp.705-709
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    • 2008
  • NF-${\kappa}B$ is a transcriptional regulator involved in many biological processes including proliferation, survival, and differentiation. Recently, we reported that expression and activity of NF-${\kappa}B$ is comparatively low in undifferentiated human embryonic stem (ES) cells, but increases during differentiation. Here, we found a lower expression of NF-${\kappa}B$ p65 protein in mouse ES cells when compared with mouse embryonic fibroblast cells. Protein levels of NF-${\kappa}B$ p65 and relB were clearly enhanced during retinoic acid-induced differentiation. Furthermore, increased DNA binding activity of NF-${\kappa}B$ in response to TNF-$\alpha$, an agonist of NF-${\kappa}B$ signaling, was seen in differentiated but not undifferentiated mouse ES cells. Taken together with our previous data in human ES cells, it is likely that NF-${\kappa}B$ expression and activity of the NF-${\kappa}B$ signaling pathway is comparatively low in undifferentiated ES cells, but increases during differentiation of ES cells in general.

Peroxisome proliferator-activated receptor $\alpha$(PPAR$\alpha$) and its clinical significance

  • 윤미정
    • The Zoological Society Korea : Newsletter
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    • v.18 no.2
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    • pp.6-11
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    • 2001
  • Peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$)에 대한 본격적인 연구는 고지혈증 치료제인 fibrate류의 약물들이 PPAR$\alpha$ activator로 작용한다는 사실이 밝혀짐으로써 크게 증대되었다. PPAR$\alpha$는 fibrate를 포함한 다양한 종류의 peroxisome proiferator (PP)에 의해 활성화되는데 이들을 쥐에 단기간 투여할 경우 간의 peroxisome수와 지 방산 산화효소의 유전자발현이 증가되고 장기간 투여 할 경우 간암을 발생시키지만, fibrate류의 약물들을 고지혈증 환자에게 투여 할 경우 간암을 발생시키지 않으므로써 PP에 대한 반응성에 있어서 species difference를 나타낸다 PPAR$\alpha$는 핵에 존재하는 orphan receptor로서 PP에 의해 활성화되어 9-cis-retinoic acid receptor(RXR)와 heterodimer를 이룬 후 target gene들의 upstream에 있는 peroxisome proliferator response element (PPRE)에 결합하여 target gene들의 발현을 조절한다. 지금까지 연구된 PPAR$\alpha$의 target gene들은 모두 lipid와 lipoprotein 대사를 조절하는 것으로 알려져 있으며, 이러 한 결과들을 기초로 lipid 대사 및 energy balance와 관련된 질병들 - 동맥경화증, 관상동맥질환, 비만, 제 2형 당뇨병 등에서 PPAR$\alpha$의 역할이 집중적으로 연구되고 있다. PPAR$\alpha$가 활성화되면 lipoprotein lipase와 HDL이 증가되고 apo C-III가 감소됨으로써 동맥경화증에 대한 예방적 기능을 나타내고, 몸무게를 감소시킴으로써 비만을 방지할 수 있으며, 인슐린 감수성을 증가시켜 제 2형 당뇨병의 치료효과를 가지는 것으로 보인다. 그러나 PPAR$\alpha$-null mouse에서는 이러한 효과들이 나타나지 않는 것으로 보아 이들 질병에서 PPAR$\alpha$가 중요한 역할을 하는 것으로 생각된다.

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