• Title/Summary/Keyword: translocation

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Induction of Apoptosis by HDAC Inhibitor Trichostatin A through Activation of Caspases and NF-κB in Human Prostate Epithelial Cells. (인체 전립선 상피세포에서 HDAC 저해제 trichostatin A의 caspase 및 NF-κB의 활성화를 통한 apoptosis 유도)

  • Park, Cheol;Jin, Cheng-Yun;Choi, Byung-Tae;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.18 no.3
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    • pp.336-343
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    • 2008
  • Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.

Anti-inflammatory Activities of Methanolic Extracts from Different Rose Cultivars (품종별 장미꽃 메탄올 추출물의 항염증 효과)

  • Lee, Seon-Mi;Li, Lin;Sung, Jeehye;Yang, Jinwoo;Kim, Younghwa;Jeong, Heon Sang;Lee, Junsoo
    • The Korean Journal of Food And Nutrition
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    • v.28 no.4
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    • pp.551-557
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    • 2015
  • The genus Rosa (Rosaceae) is an abundant source of phenolics and is traditionally used as a food supplement and as herbal medicine. Various plant phenolics are known to have anticancer, antioxidant, and anti-inflammatory properties. In this study, we investigated the anti-inflammatory effects of rose methanolic extracts (RMEs) from four different rose cultivars (Macarena, Onnuri, Oklahoma, and Colorado) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Our results demonstrated that pretreatment of REMs ($500{\mu}g/mL$) significantly reduced NO production by suppressing iNOS protein expression in LPS-stimulated cells. Anti-inflammatory effects by RMEs were observed in the following order: Oklahoma > Colorado > Onnuri > Macarena. Consistent with this finding, RMEs inhibited the translocation of $NF-{\kappa}B$ from the cytosol to the nucleus via the suppression of $I{\kappa}B{\alpha}$ phosphorylation and also inhibited LPS-stimulated $NF-{\kappa}B$ transcriptional activity. These findings suggest that RMEs exert anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of RMEs. Therefore, RMEs could be regarded as a potential source of natural anti-inflammatory agents.

Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice

  • Kim, Kyung Eun;Kim, Hwajin;Heo, Rok Won;Shi, Hyun Joo;Yi, Chin-ok;Lee, Dong Hoon;Kim, Hyun Joon;Kang, Sang Soo;Cho, Gyeong Jae;Choi, Wan Sung;Roh, Gu Seob
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.451-460
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    • 2015
  • Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice

  • Park, Ji-Won;Ryu, Hyung Won;Ahn, Hye In;Min, Jae-Hong;Kim, Seong-Man;Kim, Min-Gu;Kwon, Ok-Kyoung;Hwang, Daseul;Kim, Soo-Yong;Choi, Sangho;Zamora, Nelson;Rosales, Kattia;Oh, Sei-Ryang;Lee, Jae-Won;Ahn, Kyung-Seop
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1614-1625
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    • 2020
  • A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Uptake and Tolerance to Lead in Populus alba × glandulosa and Betula Schmidtii (현사시와 박달나무의 Pb 흡수능력(吸收能力) 및 내성(耐性))

  • Yeo, Jin Kie;Kim, In Sik;Koo, Yeong Bon;Lee, Jae Chun
    • Journal of Korean Society of Forest Science
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    • v.90 no.5
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    • pp.600-607
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    • 2001
  • This study was conducted to estimate the capability of Populus alba ${\times}$ glandulosa and Betula schmidtii for the uptake of Pb from the lead-contaminated soil and their tolerance to lead. Rooted cuttings in the former species and germinated seedlings in the latter species were planted in pots and irrigated with Pb-containing water for 60 days. In both tree species, growth inhibition was observed in 800, and 1,500ppm of $Pb(NO_3)_2$. Most Pb was accumulated in plant roots and only a small portion was transported to the shoots. The translocation rates of Pb for B. schmidtii and P. alba ${\times}$ glandulosa were 1.6-2.6% and 1.2-1.6%, respectively. The maximum Pb content accumulated in shoots was 468.0mg/kg d.w. in P. alba ${\times}$ glandulosa, and 602.0mg/kg d.w. in B. schmidtii. Although tolerance to lead was generally higher in B. schmidtii than P. alba ${\times}$ glandulosa, the highest tolerance to lead was observed in P. alba ${\times}$ glandulosa clone, 72-16. Finally, we discussed the applicability of P. alba ${\times}$ glandulosa and B. schmidtii for phytoextraction based on their Pb uptake ability, high biomass production, and easiness in large-scale cultivation.

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The Effects of Anti-Inflammatory Activities and Active Fractions Analysis of Ethanol Extract from Red Rose Petals (붉은 장미꽃잎 에탄올 추출물의 활성 분획물 분석 및 항염증 활성 효과)

  • Kim, Hyun Kyoung
    • The Journal of the Convergence on Culture Technology
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    • v.6 no.2
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    • pp.543-551
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    • 2020
  • Red rose petals are usually disposed but they are an abundant source of phenolics and traditionally used as food supplement and as herbal medicine. Of the Various phenolics, they are known to have anticancer, antioxidant, and anti-inflammatory properties. In this study, we investigated the anti-inflammatory effects of red rose ethanolic extracts(GRP) on lipopolysaccharide (LPS)-activated RAW 264.7 cells. The results demonstrated that pretreatment of GRP(500㎍/mL) significantly reduced NO production by suppressing iNOS protein expression in LPS-stimulated cells. Anti-inflammatory effects byred rose petal were observed in the following. Red rose petal inhibited the translocation of NF-κB from the cytosol to the nucleus via the suppression of IκB-α phosphorylation and also inhibited LPS-stimulated NF-κB transcriptional activity. These findings suggest that red rose petal exert anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of red rose petal. Therefore, red rose petal could be regarded as a potential source of natural anti-inflammatory agents.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice

  • Shin, Eun-Ju;Shin, Seul-Mee;Kong, Hyun-Seok;Lee, Sung-Won;Do, Seon-Gil;Jo, Tae-Hyung;Park, Young-In;Lee, Chong-Kil;Hwang, In-Kyeong;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • v.11 no.2
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    • pp.107-113
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    • 2011
  • Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

Anti-Inflammatory Effects of 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose in LPS-Stimulated Macrophages (LPS로 자극한 대식세포에서 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose의 염증 억제 효과)

  • Lee, Hee Won;Kang, Ye Rim;Bae, Min Seo;Kim, Yoon Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.409-416
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    • 2017
  • 1,2,3,4,6-Penta-O-galloyl-${\beta}$-D-glucose (PGG) is a gallotannin isolated from Galla Rhois. In a previous study, PGG was shown to suppress the allergic response by attenuating immunoglobulin E production both in vitro and in vivo. However, the effect of PGG on bacteria-induced inflammation at physiological concentration remains unclear. Therefore, the aim of this study was to investigate the effect of PGG on lipopolysaccharide (LPS)-stimulated macrophages. PGG inhibited release of nitric oxide (NO) and prostaglandin $E_2$ by alleviating protein expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Furthermore, PGG suppressed the release of interleukin-6 and tumor necrosis factor-${\alpha}$ induced by LPS. Further study indicated that PGG blocked translocation of the p65 subunit of nuclear factor-${\kappa}B$ from the cytosol into the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of PGG. Collectively, these data suggest that PGG might be useful for the treatment of inflammatory disease.

Improvement on the Method of Estimating Radionuclide Concentrations in Agricultural Products for the Off-Site Internal Dose Calculation for Operating Nuclear Facilities (가동중 원자력 시설 주변 주민의 내부피폭선량 계산을 위한 농산물내 핵종 농도 평가법 개선)

  • Choi, Y.H.;Lim, K.M.;Hwang, W.T.;Choi, G.S.;Choi, H.J.;Lee, C.W.
    • Journal of Radiation Protection and Research
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    • v.29 no.2
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    • pp.73-90
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    • 2004
  • The Reg. Guide 1.109 model was reviewed against its applicability to calculating radionuclide concentrations in agricultural products for operating nuclear facilities and an improved method was proposed. The model was so modified that the radionuclides deposited since the start of operation could be considered in assessing the root uptake. Translocation factors were introduced in the equation for calculating the concentrations in edible parts due to direct plant deposition. Values specific to Korea were set up for the input parameters of the modified model. The concentrations of $^{54}Mn,\;^{60}Co,\;^{90}Sr\;and\;^{137}Cs$ in rice seeds, Chinese cabbage and radish root were calculated for various hypothetical deposition histories using the Reg. Guide 1.109 model and the modified model with parameter values in the guide and those specific to Korea put in alternately. Through comparisons among the results, it could be expected that the use of the modified model with the input of parameter values specific to Korea would result In a more resonable and realistic assessment.

A Case of Lung Metastasis of Mesoblastic Nephroma in Adulthood (성인에서 발생한 중배엽성 신종의 폐전이 1예)

  • Moon, Jin Wook;Kim, Kil Dong;Shin, Dong Hwan;Hahn, Chang Hoon;Jung, Jae;Park, Mu Suk;Jung, Sang Youn;Lee, Jae Hyuk;Kim, Young Sam;Kim, Se Kyu;Kim, Sung Kyu;Chang, Joon
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.4
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    • pp.402-407
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    • 2003
  • Mesoblastic nephroma is a neoplasm of the kidney which is characterized by interlacing bundles of spindle mesenchymal cells. It is usually diagnosed during the first six months of life and is mostly benign. Incidence in adults is exceedingly rare. In most cases, only total excision is required without postoperative adjuvant therapy, and the rare cases of local recurrence have usually been related to incomplete removal. However, mesoblastic nephroma may behave aggressively, in contrast to a congenital mesoblastic nephroma. Several cases of metastatic mesoblastic nephroma have been previously described. We report herein a case of a 42-year-old woman with mesoblastic nephroma which recurred as a large metastatic lung mass seven years after the nephrectomy. The patient presented with chest wall discomfort for four days. Seven years previously, total nephrectomy had been performed because of a right renal tumor which had been diagnosed as a mesoblastic nephroma. There had been no evidence of recurrence for five years, after which she discontinued follow-up. On readmission two years later, chest X-ray and CT scan revealed a large lung mass in the left upper lobe. It was completely excised and the pathologic examination was identical with that of the original renal tumor. Synovial sarcoma was excluded because the fusion transcripts of the SYT-SSX fusion gene associated with the t(X;18) translocation were negative. The final diagnosis was a lung metastasis of mesoblastic nephroma and the patient remained free of disease for 7 months postoperatively.