• Title/Summary/Keyword: transcription activator

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Photoaging protective effects of BIOGF1K, a compound-K-rich fraction prepared from Panax ginseng

  • Hong, Yo Han;Kim, Donghyun;Nam, Gibaeg;Yoo, Sulgi;Han, Sang Yun;Jeong, Seong-Gu;Kim, Eunji;Jeong, Deok;Yoon, Keejung;Kim, Sunggyu;Park, Junseong;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.81-89
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    • 2018
  • Background: BIOGF1K, a compound-K-rich fraction, has been shown to display anti-inflammatory activity. Although Panax ginseng is widely used for the prevention of photoaging events induced by UVB irradiation, the effect of BIOGF1K on photoaging has not yet been examined. In this study, we investigated the effects of BIOGF1K on UVB-induced photoaging events. Methods: We analyzed the ability of BIOGF1K to prevent UVB-induced apoptosis, enhance matrix metalloproteinase (MMP) expression, upregulate anti-inflammatory activity, reduce sirtuin 1 expression, and melanin production using reverse transcription-polymerase chain reaction, melanin content assay, tyrosinase assay, and flow cytometry. We also evaluated the effects of BIOGF1K on the activator protein-1 signaling pathway, which plays an important role in photoaging, by immunoblot analysis and luciferase reporter gene assays. Results: Treatment of UVB-irradiated NIH3T3 fibroblasts with BIOGF1K prevented UVB-induced cell death, inhibited apoptosis, suppressed morphological changes, reduced melanin secretion, restored the levels of type I procollagen and sirtuin 1, and prevented mRNA upregulation of MMP-1, MMP-2, and cyclo-oxygenase-2; these effects all occurred in a dose-dependent manner. In addition, BIOGF1K markedly reduced activator-protein-1-mediated luciferase activity and decreased the activity of mitogen-activated protein kinases (extracellular response kinase, p38, and C-Jun N-terminal kinase). Conclusion: Our results strongly suggest that BIOGF1K has anti-photoaging activity and that BIOGF1K could be used in anti-aging cosmeceutical preparations.

Effects of Sulraphane on Osteoclastogenesis in RAW 264.7 (RAW 264.7 세포에서 sulforaphane의 파골세포형성 저해효과)

  • Hwang, Joon-Ho;Yi, Mi-Ran;Kang, Chang-Hee;Bu, Hee-Jung
    • Journal of agriculture & life science
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    • v.50 no.2
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    • pp.151-160
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    • 2016
  • Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Sulforaphane, isolated from the Broccoli(Brassica oleracea var. italia) florets, inhibits the production of inflamatory cytokine. In the present study, we determined inhibitory effect of sulforaphane on Receptor activator of nuclear factor κB ligand(RANKL)-induced osteoclast formation. Sulforaphane inhibited the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase(TRAP), cathepsin K, matrix metalloproteinase 9(MMP-9), and calcitonin receptor in RANKL-induced RAW 264.7 macrophage. Also, sluforaphane inhibited the expression of osteoclast protein, such as TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6) and transcription factor nuclease factor of activated T cells(NFAT)c1. Sulforaphane inhibited RANKL-induced activiation of nuclear factor kappaB(NF-kappaB) by suppression RANKL-mediated NF-kappaB transcriptional acitivation. We are confirmed that sulforaphane inhibits not only transcriptional activity of NF-kappaB but also expressions of the osteoclastogenesis factors(TRAP, cathepsin K, MMP-9, calcitonin, TRAF6) and trranscription factor NFATc1.

Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor (ATBF1) Gene

  • Zhang, Xiaoyan;Wu, Xianfeng;Jia, Wenchao;Pan, Chuanying;Li, Xiangcheng;Lei, Chuzhao;Chen, Hong;Lan, Xianyong
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.10
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    • pp.1394-1406
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    • 2015
  • The AT motif-binding factor (ATBF1) not only interacts with protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) to suppress STAT3 signaling regulating embryo early development and cell differentiation, but is required for early activation of the pituitary specific transcription factor 1 (Pit1) gene (also known as POU1F1) critically affecting mammalian growth and development. The goal of this study was to detect novel nucleotide variations and haplotypes structure of the ATBF1 gene, as well as to test their associations with growth-related traits in goats. Herein, a total of seven novel single nucleotide polymorphisms (SNPs) (SNP 1-7) within this gene were found in two well-known Chinese native goat breeds. Haplotypes structure analysis demonstrated that there were four haplotypes in Hainan black goat while seventeen haplotypes in Xinong Saanen dairy goat, and both breeds only shared one haplotype (hap1). Association testing revealed that the SNP2, SNP5, SNP6, and SNP7 loci were also found to significantly associate with growth-related traits in goats, respectively. Moreover, one diplotype in Xinong Saanen dairy goats significantly linked to growth related traits. These preliminary findings not only would extend the spectrum of genetic variations of the goat ATBF1 gene, but also would contribute to implementing marker-assisted selection in genetics and breeding in goats.

Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for pluripotency and self-renewal of mouse embryonic stem cells via downregulation of Nanog transcription

  • Kang, Songhwa;Yun, Jisoo;Kim, Da Yeon;Jung, Seok Yun;Kim, Yeon Ju;Park, Ji Hye;Ji, Seung Taek;Jang, Woong Bi;Ha, Jongseong;Kim, Jae Ho;Baek, Sang Hong;Kwon, Sang-Mo
    • BMB Reports
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    • v.51 no.2
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    • pp.92-97
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    • 2018
  • B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the $NF-{\kappa}B$ family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity.

Flavonoid Luteolin Inhibits LPS-induced Type I Interferon in Primary Macrophages (플라보노이드 루테올린의 lippopolysacharide로 유도한 type 1 interferon 억제 효과)

  • Jung, Won-Seok;Bae, Gi-Sang;Cho, Chang-Re;Park, Kyoung-Chel;Koo, Bon-Soon;Kim, Min-Sun;Ham, Kyung-Wan;Jo, Beom-Yeon;Cho, Gil-Hwan;Seo, Sang-Wan;Lee, Si-Woo;Song, Ho-Joon;Park, Sung-Joo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.986-992
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    • 2009
  • Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

Bacterial Hash Function Using DNA-Based XOR Logic Reveals Unexpected Behavior of the LuxR Promoter

  • Pearson, Brianna;Lau, Kin H.;Allen, Alicia;Barron, James;Cool, Robert;Davis, Kelly;DeLoache, Will;Feeney, Erin;Gordon, Andrew;Igo, John;Lewis, Aaron;Muscalino, Kristi;Parra, Madeline;Penumetcha, Pallavi;Rinker, Victoria G.;Roland, Karlesha;Zhu, Xiao;Poet, Jeffrey L.;Eckdahl, Todd T.;Heyer, Laurie J.;Campbell, A. Malcolm
    • Interdisciplinary Bio Central
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    • v.3 no.3
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    • pp.10.1-10.8
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    • 2011
  • Introduction: Hash functions are computer algorithms that protect information and secure transactions. In response to the NIST's "International Call for Hash Function", we developed a biological hash function using the computing capabilities of bacteria. We designed a DNA-based XOR logic gate that allows bacterial colonies arranged in a series on an agar plate to perform hash function calculations. Results and Discussion: In order to provide each colony with adequate time to process inputs and perform XOR logic, we designed and successfully demonstrated a system for time-delayed bacterial growth. Our system is based on the diffusion of ${\ss}$-lactamase, resulting in destruction of ampicillin. Our DNA-based XOR logic gate design is based on the op-position of two promoters. Our results showed that $P_{lux}$ and $P_{OmpC}$ functioned as expected individually, but $P_{lux}$ did not behave as expected in the XOR construct. Our data showed that, contrary to literature reports, the $P_{lux}$ promoter is bidirectional. In the absence of the 3OC6 inducer, the LuxR activator can bind to the $P_{lux}$ promoter and induce backwards transcription. Conclusion and Prospects: Our system of time delayed bacterial growth allows for the successive processing of a bacterial hash function, and is expected to have utility in other synthetic biology applications. While testing our DNA-based XOR logic gate, we uncovered a novel function of $P_{lux}$. In the absence of autoinducer 3OC6, LuxR binds to $P_{lux}$ and activates backwards transcription. This result advances basic research and has important implications for the widespread use of the $P_{lux}$ promoter.

Effect of Fucoidan on Angiogenesis and Gene Expression in Human Umbilical Vein Endothelial Cells (후코이단이 혈관 내피세포의 신생혈관 생성 효과 및 관련 유전자의 발현에 미치는 영향)

  • Park, Ho;Kim, Beom-Su
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.4
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    • pp.323-328
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    • 2017
  • Angiogenesis is a process including members of the angiogenic factors. In particular, fibroblast growth factor 2 (FGF2) is considered the most potent angiogenic factor because it promotes cell proliferation and tube formation. A recent study reported that fucoidan derived from marine plant potentiated FGF-2 induced tube formation in human endothelial cells. On the other hand, the molecular mechanisms involved in the angiogenic activity of fucoidan and FGF2 are unknown. In this study, a fucoidan treatment promoted angiogenesis induced by FGF2. The effects of fucoidan on FGF2-induced angiogenesis were confirmed by a proliferation assay using a CellTiter96 Aqueous One solution after a treatment with fucoidan and FGF2. The tube formation and wound healing assay for the angiogenic activity were also confirmed. Reverse transcription PCR showed a change in the mRNA of vascular endothelial growth factor-A (VEGF-A), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase9 (MMP9), and the signal transducer and activator of transcription3 (STAT3). In summary, the Fucoidan/FGF2 treatment induced an increase in cell proliferation, improved the tube formation and wound healing activity, and altered the STAT3, VEGF-A, ICAM-1, and MMP9 mRNA expression levels. Further research will be needed to provide a scientific explanation in terms of cell-signaling and confirm the present findings.

miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells

  • Ning Song;Jun Luo;Lian Huang;Xiaoying Chen;Huimin Niu;Lu Zhu
    • Animal Bioscience
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    • v.36 no.10
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    • pp.1488-1498
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    • 2023
  • Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

Induction Patterns of Suppressor of Cytokine Signaling (SOCS) by Immune Elicitors in Anopheles sinensis

  • Noh Mi-Young;Jo Yong-Hun;Lee Yong-Seok;Kim Heung-Chul;Bang In-Seok;Chun Jae-Sun;Lee In-Hee;Seo Sook-Jae;Shin E-Hyun;Han Man-Deuk;Kim Ik-Soo;Han Yeon-Soo
    • International Journal of Industrial Entomology and Biomaterials
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    • v.12 no.2
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    • pp.57-61
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    • 2006
  • Suppressor of cytokine signaling (SOCS) is known to be as a negative feedback regulator in Janus kinase signal transducer and activator of transcription signaling. Highly conserved SOCS box domain was cloned from a Korean malaria vector, Anopheles sinensis. Sequence analysis indicates that it has identity to Anopheles gambiae (96%), Aedes aegypti (94%), Drosophila melanogaster (78%), Mus musculus (72%) and Homo sapiens (72%), respectively. Tissue specificity RT-PCR demonstrated that the expression level of AsSOCS transcript was high at abdomen, midgut, and ovary, whereas developmental expression patterns showed that the level of AsSOCS was high at egg, early pupae, and adult female. On the other hand, RT-PCR analysis after bacterial challenge showed that SOCS mRNA was strongly induced in larvae. In addition, it was also induced by various immune elicitors such as lipoteicoic acid, CpG-DNA, and laminarin. It seems that AsSOCS, repressor of JAK-STAT pathway, is highly conserved in mosquito, and may play an important role in mosquito innate immune response.

Identification of HUGT1 as a Potential BiP Activator and a Cellular Target for Improvement of Recombinant Protein Production Using a cDNA Screening System

  • Ku, Sebastian Chih Yuan;Lwa, Teng Rhui;Giam, Maybelline;Yap, Miranda Gek Sim;Chao, Sheng-Hao
    • Molecules and Cells
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    • v.27 no.5
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    • pp.577-582
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    • 2009
  • The development of a high-throughput functional genomic screening provides a novel and expeditious approach in identifying critical genes involved in specific biological processes. Here we describe a cell-based cDNA screening system to identify the transcription activators of BiP, an endoplasmic reticulum (ER) chaperone protein. BiP promoter contains the ER stress element which is commonly present in the genes involved in unfolded protein response (UPR) that regulates protein secretion in cells. Therefore, the positive regulators of BiP may also be utilized to improve the recombinant protein production through modulation of UPR. Four BiP activators, including human UDP-glucose:glycoprotein glucosyltransferase 1 (HUGT1), are identified by the cDNA screening. Overexpression of HUGT1 leads to a significant increase in the production of recombinant erythropoietin, interferon ${\gamma}$, and monoclonal antibody in HEK293 cells. Our results demonstrate that the cDNA screening for BiP activators may be effective to identify the novel BiP regulators and HUGT1 may serve as an ideal target gene for improving the recombinant protein production in mammalian cells.