• Title/Summary/Keyword: translocation

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8-60hIPP5m-Induced G2/M Cell Cycle Arrest Involves Activation of ATM/p53/p21cip1/waf1 Pathways and Delayed Cyclin B1 Nuclear Translocation

  • Zeng, Qi-Yan;Zeng, Lin-Jie;Huang, Yu;Huang, Yong-Qi;Zhu, Qi-Fang;Liao, Zhi-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.4101-4107
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    • 2014
  • Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of $8-60hIPP5^m$ in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of $8-60hIPP5^m$ induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, $p21^{cip1/waf1}$ and Cdc2, suggesting that $8-60hIPP5^m$ induces G2/M arrest through activation of the ATM/p53/$p21^{cip1/waf1}$/Cdc2/cyclin B1 pathways. We further showed that overexpression of $8-60hIPP5^m$ led to delayed nuclear translocation of cyclin B1. $8-60hIPP5^m$ also could translocate to the nucleus in G2/M phase and interact with $pp1{\alpha}$ and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for $8-60hIPP5^m$ in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

  • Kwon, Seung-Hwan;Ma, Shi-Xun;Hwang, Ji-Young;Ko, Yong-Hyun;Seo, Ji-Yeon;Lee, Bo-Ram;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.268-282
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    • 2016
  • In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

Inhibitory Effects of β-Glycyrrhetinic Acid on Tumor Necrosis Factor-α Production in RAW 264.7 Cells

  • Park, Kyoung-Sik
    • Journal of Applied Biological Chemistry
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    • v.53 no.3
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    • pp.147-153
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    • 2010
  • $\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

Relationship between Leaf Senescence and Photosynthate Translocation during Grain filling in Barley (대맥의 등숙기간중 엽신의 노화와 동화산물의 전류와의 관계)

  • 남윤일;구본철;연규복;맹돈재
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.36 no.1
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    • pp.34-40
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    • 1991
  • The study aimed to investigate the relationship between the rates of leaf senescence and photosynthate translocation at post-anthesis. Seven barley varieties were observed at Suweon in 1988-89. The varieties differed significantly in the number of leaves survived and the rate of photosynthate transolcation with the progress of grain filling. The rate of grain filling was higher in the fast leaf sene-scencing varieties than the slow senescencing ones. There was a close coincidence between the rates of grain filling and $\^$14/c translocation into grains. Photosynthesis was higher in the fast leaf senescencing varieties at early stage of grain filling, but the reverse phenomenon was observed at the late stage of grain filling. The grain yield of fast senescencing varieties was higher than that of slow ones.

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Alteration of macronutrients, metal translocation and bioaccumulation as potential indicators of nickel tolerance in three Vigna species

  • Ishtiaq, Shabnam;Mahmood, Seema;Athar, Mohammad
    • Advances in environmental research
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    • v.3 no.1
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    • pp.71-86
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    • 2014
  • Macronutrients ($Na^+$, $K^+$, $Ca^{2+}$, $Mg^{2+}$), yield and yield components, bioaccumulation and translocation of metal in plant parts of three Vigna species (V. cylindrica, V. mungo, V. radiata) were evaluated at 0, 50, 100 and $150mgkg^{-1}$ soil of Nickel (Ni). A marked inhibition (p < 0.001) in the distribution of various macronutrients was noticed in these Vigna species except for $Mg^{2+}$ content of the shoot and leaves. Similarly, all species retained more $Ca^{2+}$ in their roots (p < 0.05) as compared to the aerial tissues. Ni induced a drastic decline (p < 0.001) for various yield and yield attributes except for 100 seed weight. Toxicity and accumulation of Ni in plant tissues considerably increased in a concentration dependent manner. Vigna species signify an exclusion approach for Ni tolerance as both bioaccumulation factor (BF) and translocation factor (TF) were less than 1.0. The Ni content of plants being root > shoot > leaves > seeds. Scoring for percentage stimulation and inhibition (respective to control) at varying levels of Ni revealed tolerance of the species in an order of V. radiata > V. cylindrica > V. mungo. The acquisition of Ni tolerance in V. radiata seems to occur through an integrated mechanism of metal tolerance that includes sustainable macronutrients uptake, stronger roots due to greater deposition of $Ca^{2+}$in the roots, restricted transfer of Ni to above ground tissues and seeds as well as exclusion capacity of the roots to bind appreciable amount of metal to them. Thus, metal tolerant potential of V. radiata could be of great significance to remediate metal contaminated soil owing lesser impact of Ni on macro-nutrients, hence the yield.

FUSION OF THE PLAG1 AND CTNNB1 GENES IN PLEOMORPHIC ADENOMA OF THE SALIVARY GLANDS (타액선 다형성 선종에서의 PLAG1과 CTNNB1 유전자 융합)

  • Kim, Jae-Jin;Kim, Eun-Seok;Ko, Seung-O;Kim, Hyo-Bun;Cho, Nam-Pyo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.29 no.4
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    • pp.206-211
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    • 2003
  • The pleomorphic adenoma is the most common neoplasm involving both the major and minor salivary glands. It is a benign, slowgrowing tumor, but local recurrences can occur. The pleomorphic adenoma gene 1 (PLAG1), which is a novel zinc finger gene, is frequently activated by reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. This experimental study was preformed to observe the translocation patterns between PLAG1 gene and the three translocation partner genes. We also have analyzed the presence of PLAG1 transcripts by RT-PCR. CTNNB1/PLAG1 gene fusion was observed in three of nine pleomorphic adnomas. However, LIFR/PLAG1 and SII/PLAG1 gene fusions were not detectable. All of three gene fusions was not detectable in one Warthin's tumor and three inflammatory salivary gland tissues. PLAG1 transcripts were expressed in all inflammatory salivary gland tissues and tumors except for three pleomorphic adenomas. Of particular one pleomorphic adenoma showing CTNNB1/PLAG1 gene fusion did not express PLAG1 transcipt. Our data indicate that gene fusion involving PLAG1 is a frequent event in pleomorphic adenoma, but correlation between gene fusion involving PLAG1 and PLAG1 transcription is not definite.

Defecation of Norovirus from the Oyster Crassostrea gigas by Depuration Following Translocation of the Growing Area (자연정화에 의한 양식굴(Crassostrea gigas) 중 노로바이러스 저감화)

  • Yu, Hongsik;Park, Yong Su;An, Sera;Park, Kunbawui;Shim, Kil Bo;Song, Ki Cheol;Lee, Tae Seek
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.49 no.2
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    • pp.109-115
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    • 2016
  • The efficacy of depuration following growing area translocation for the defecation of norovirus was evaluated under experimental conditions using oysters Crassostrea gigas previously subjected to bioaccumulation of this virus at a waste treatment plant discharge site. Three trials were assayed in an open experimental system with a commercial oyster farm located in a shellfish growing area approved by the Korean Shellfish Sanitation Program. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to quantify viruses in the digestive glands of oysters. The final viral loads in oysters after 12 days remained under the detection limit (10 copies/g digestive gland) of the real-time RT-PCR. This reduction trend showed two-phase removal kinetics, with an initial slow reduction or slight increase in viruses during the first 2 days of depuration and subsequent stabilization with 0.12 to 2.64 log unit norovirus copies/g digestive gland per 2 days of depuration for the remaining time.

The Enhanced Monocyte Adhesiveness after UVB Exposure Requires ROS and NF-κB Signaling in Human Keratinocyte

  • Park, Lee-Jin;Ju, Sung-Mi;Song, Ha-Yong;Lee, Ji-Ae;Yang, Mi-Young;Kang, Young-Hee;Kwon, Hyung-Joo;Kim, Tae-Yoon;Choi, Soo-Young;Park, Jin-Seu
    • BMB Reports
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    • v.39 no.5
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    • pp.618-625
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    • 2006
  • The infiltration of both monocyte and activated T cells in the skin is one of critical steps in the development of UVB-induced inflammation. Upregulation of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) on the surface of keratinocytes plays an important role in this process. In this study, we examined the molecular mechanism responsible for UVB-induced expression of ICAM-1 and subsequent monocyte adhesion by keratinocyte. We observed that (1) UVB induced protein and mRNA expression of ICAM-1 in a dose- and time-dependent manner in human keratinocyte cell HaCaT; (2) UVB induced the translocation of NF-kappaB and inhibition of NF-kappaB by NF-kappaB inhibitors suppressed UVB-induced mRNA and protein expression of ICAM-1; (3) UVB increased the intracellular level of reactive oxygen species (ROS) by HaCaT cells; (4) UVB-induced increase of intracellular ROS level was suppressed by pre-treatment with diphenyl iodonium (DPI) and N-acetyl cysteine (NAC); and (5) inhibition of UVB-induced ROS production by DPI or NAC suppressed UVB-mediated translocation of NF-kappaB, expression of ICAM-1 and subsequent monocyte adhesion in HaCaT cells. These results suggest that UVB-induced ROS is involved in the translocation of NF-kappaB which is responsible for expression of ICAM-1 and subsequent increased monocyte adhesion in human keratinocyte.

Effects of Oenanthe javanica on Transcriptional Regulation of COX-2 by Inhibiting Translocation of p65 Subunit in LPS-Stimulated Murine Peritoneal Macrophages

  • Lee, Jeong-Min;Kim, Hyun-Ji;Choi, Hee-Jung;You, Yang-Hee;Hwang, Kwon-Tack;Lee, Myung-Yul;Park, Chang-Soo;Jun, Woo-Jin
    • Food Science and Biotechnology
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    • v.15 no.6
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    • pp.975-979
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    • 2006
  • The extracts of Oenanthe javanica were evaluated for their effects on the expression of cyclooxygenase-2 (COX-2), which is mediated by the translocation of the p65 subunit into the nucleus. Fractions of ethyl acetate and chloroform from 80% ethanol extracts of O. javanica exhibited inhibitory effects on the secretion of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) from lipopolysaccharide (LPS)-stimulated peritoneal macrophages; however, the aqueous- and hexane-fractions showed no significant effect. The ethyl acetate- and chloroform-fractions also reduced the COX-2 enzyme levels after 24-hr treatment. RT-PCR showed that the mRNA levels of COX-2 decreased following treatment with these fractions, suggesting that COX-2 expression is transcriptionally regulated by these extracts. We examined the effects of the chloroform- and ethyl acetate-fractions on the cytosolic activation of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$, p65 subunit) and on the degradation of inhibitor-${\kappa}B{\alpha}$ ($I-{\kappa}B{\alpha}$) in order to determine the mechanism of COX-2 regulation. The LPS-stimulated activation of the p65 subunit was significantly blocked upon the addition of $50\;{\mu}g/mL$ of these fractions, and the cytosolic $I-{\kappa}B{\alpha}$ degradation process was simultaneously inhibited. These findings suggest that the inhibition of COX-2 expression by the ethyl acetate-and chloroform-fractions may result from the inhibition of p65 translocation by blocking the degradation of $I-{\kappa}B{\alpha}$; this may be the mechanistic basis for the anti-inflammatory effects of O. javanica.

Aortic Translocation for Complete Transposition of the Great Arteries with a Ventricular Septal Defect and Pulmonic Stenosis (심실 중격 결손과 폐동맥 협착을 동반한 완전 대혈관 전위에서 대동맥 전위술)

  • Jeong, In-Seok;Lee, Chang-Ha;Lee, Cheul;Lim, Hong-Gook;Kim, In-Sub;Youn, Hyo-Chul
    • Journal of Chest Surgery
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    • v.41 no.4
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    • pp.476-479
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    • 2008
  • The Rastelli operation has been a standard procedure for repairing complete transposition of the great arteries combined with a ventricular septal defect and pulmonary stenosis. Yet this procedure has several shortcomings, including the risk of incurring left ventricular outflow tract obstruction on long-term follow-up. In this regard, aortic translocation has recently been regarded as a potent alternative to Rastelli's operation. We report here on a case of complete transposition of the great arteries that was combined with an inlet-extended perimembranous ventricular septal defect and pulmonary stenosis in a 2-year-old boy. All the problems were successfully repaired using the aortic translocation technique. Postoperative echocardiography showed a straight and wide left ventricular outflow tract.