• 제목/요약/키워드: Small G protein

검색결과 401건 처리시간 0.035초

Molecular Mechanisms of Cell Cycle Arrest and Apoptosis by Dideoxypetrosynol A, a Polyacetylene from the Sponge Petrosia sp., in Human Monocytic Leukemia Cells

  • Choi, Yung Hyun
    • 한국해양바이오학회지
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    • 제1권4호
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    • pp.243-251
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    • 2006
  • Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, however, the mechanisms of which are poorly understood. In the present study, it was investigated the further possible mechanisms by which dideoxytetrosynol A exerts its anti-proliferative action in cultured human leukemia cell line U937. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest of the cell cycle and apoptosis, which effects were associated with up-regulation of cyclin D1 and down-regulation of cyclin E without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of caspase-3 and caspase-9. Dideoxytetrosynol A decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, dideoxytetrosynol A treatment markedly inhibited the activity of telomerase, and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by dideoxytetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxytetrosynol A.

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Ginsenoside Rb1 increases macrophage phagocytosis through p38 mitogen-activated protein kinase/Akt pathway

  • Xin, Chun;Quan, Hui;Kim, Joung-Min;Hur, Young-Hoe;Shin, Jae-Yun;Bae, Hong-Beom;Choi, Jeong-Il
    • Journal of Ginseng Research
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    • 제43권3호
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    • pp.394-401
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    • 2019
  • Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.

CHANGES IN LIVE-WEIGHT GAIN, BLOOD CONSTITUENTS AND WORM EGG COUNTS IN THAI NATIVE AND CROSS-BRED GOATS RAISED IN VILLAGE ENVIRONMENTS IN SOUTHERN THAILAND

  • Kochapakdee, S.;Pralomkarn, W.;Choldumrongkul, S.;Saithanoo, S.
    • Asian-Australasian Journal of Animal Sciences
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    • 제8권3호
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    • pp.241-247
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    • 1995
  • The aim of the present study was to investigate the effect of internal parasites on growth rates of Thai Native (TN) and crossbred (75% TN $\times$ 25% Anglo-Nubian, AN and 50% TN $\times$ 50% AN) goats (undrenched, drenched every 3 weeks or at 9 weeks) in village environments in southern Thailand in a humid tropical climate. There was no significant (p > 0.05) difference in growth rate ($g/kg^{0.75}/d$) between the genotypes during unsupplemented grazing (0-64 days of the experimental period). However, during supplementary feeding (64-127 days) and throughout the period (0-127 days) TN goats had significantly (p < 0.01) lower growth rates compared with 75% TN $\times$ 25% AN and 50% TN $\times$ 50% AN goats. There was no (p > 0.05) significant difference in growth rates between 75% TN $\times$ 25% AN and 50% TN $\times$ 50 % AN goats. The growth rates of goats drenched every 3 weeks were significantly (p < 0.01) higher than those undrenched or drenched at 9 weeks. The results of this study also indicate that drenching alone did not result in increased weight gain except when the nutritional status was also improved. Parasitic infection affected some blood constituents, such as pack cell volume, haemoglobin, total protein and albumin. This resulted in lower growth rates for control groups and goats drenched at 9 weeks compared to those of goats drenched every 3 weeks.

Determination of Adequate Method for Protein Extraction from Rice Bran and the Substitution of Dried Skim Milk with Protein Concentrate from Rice Bran in Early Weaned Pigs

  • Phipek, W.;Nagasinha, C.;Vallisuth, S.;Nongyao, C.
    • Asian-Australasian Journal of Animal Sciences
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    • 제24권9호
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    • pp.1268-1273
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    • 2011
  • The present study was conducted to determine a feasible method of protein concentrate extraction from rice bran (RBPC) and its effect as a substitution for skim milk in early weaning pig diets. An investigation to extract protein concentrate from full fat rice bran was undertaken to determine the best ratio of water and rice bran, the amount of NaOH and a HCl solvent to use in a simple paddle-type mixer with modified spinning to produce RBPC. The results stated that the best ratio for water mixing in the RBPC extraction process was 1:5 with 20 g NaOH and 30 min in a paddle-type mixer at 300 rpm. A mix of 250 ml 0.2 N HCl was optimum for neutralization and protein precipitation. After the fluid was spun out with a washing machine, the sediment was left for 12-14 hours to complete the filtration. One kilogram of rice bran could produce an average of 324.5 gram RBPC and it contained 3.40% ash, 496.48 kcal of GE/100 gram, 1.94% crude fiber, 28.20% ether extract, 7.64% moisture and 16.66% crude protein, respectively. A total of 45 crossbred piglets, weaned at 3 weeks of age were allotted into control diet (A) and dietary treatments formulated with a four different rates of RBPC substitution for skim milk at a percentage of 25 (B), 50 (C), 77 (D) and 100 (E) respectively, in a randomized complete block (RCB) design. All piglets had free access to feed and water until 8 week of age when the experiment ended. Feed intake, average daily gain, growth rate and feed efficiency were not affected by dietary treatments. Blood test parameters after completion of the growth trial indicated normal health. Even though the mean of cell hemoglobin concentration was significantly different between treatments (p<0.05) it was still within the normal range. The cost difference for BW gain of 100% RBPC substituted for skim milk in the weaning diet was approximately 35% lower than that of the control and the relative cost of production was 96.67, 92.85, 70.75 and 64.48% lower for the replacement of 25, 50, 75 and 100% of skim milk respectively. These results implied that this technology is feasible for use by small scale farmers to improve their self-reliance.

Echinacea 추출물이 단구와 단구유래 수지상세포의 유전자발현에 미치는 효과 (The Effects of Echinacea Extract on the Gene Expression of Monocytes and Monocyte-derived Dendritic Cells)

  • 박준은;김성환;최강덕;함대현;서종진
    • Clinical and Experimental Pediatrics
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    • 제48권7호
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    • pp.779-788
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    • 2005
  • 목 적 : Echinacea는 면역증강제로 이미 사용되고 있는 재래 식물로서 최근에 Echinacea의 추출물로 단구를 중심으로 면역세포들에 의한 면역증강효과에 대한 연구가 이루어지고 있다. 본 연구는 단구와 수지상세포에서 Echinacea에 의해 유전자의 발현이 증가되는 면역관련 유전자들을 cDNA microarray chip을 사용하여 선별하고 이들을 토대로 Echinacea의 면역증강 효과에 대한 연구를 할 때 기초 자료가 되고자 하였다. 방 법 : 실험 1과 2는 3명의 공여자의 말초혈 단구로 실험하였는데 실험 1은 단구에 최종 농도가 $50{\mu}g/mL$ 되게 Echinacea를 첨가하여 1일간 배양하였고, 실험 2는 실험 1의 대조군으로서 Echinacea를 첨가하지 않고 배양하였다. 실험 3과 4는 2명의 공여자의 단구로 실험하였는데 실험 3은 GM-CSF와 IL-4를 첨가하여 5일간 배양시켜 수지상세포로 분화시킨 뒤 Echinacea를 첨가하여 1일간 더 배양시켰고, 실험 4는 실험 3의 대조군으로서 수지상세포로 분화시킨 뒤 Echinacea를 첨가하지 않고 1 일간 더 배양하였다. Echinacea에 의한 단구와 수지상세포의 유전자발현 효과를 알아보기 위해서 cDNA microarray chip을 이용하여 대조군에 대한 실험군의 각 유전자의 발현비를 구하였다. Echinacea를 첨가하지 않은 단구(실험 2의 단구)에 대한 Echinacea를 첨가한 단구(실험 1의 단구)의 각 유전자들의 발현 비를 구하였고, Echinacea를 첨가하지 않은 수지상세포(실험 4의 수지상세포)에 대한 Echinacea를 첨가한 수지상세포(실험 3의 수지상세포)의 각 유전자들의 발현비를 구하였다. 여기서 실험 1과 2에서는 세 공여자의 단구에서 나온 유전자 발현비의 결과를, 실험 3과 4에서는 두 공여자의 수지상세포에서 나온 유전자 발현비의 결과를 평균하여 그 발현비가 2.5 이상 되는 것을 의미있게 발현된 유전자로 보았다. 결 과 : Echinacea를 첨가하지 않은 단구를 대조군으로 하여 Echinacea를 첨가한 단구의 유전자 발현비가 2.5 이상으로 증가한 것들 중 면역과 관계된 유전자들은 17개였다. Echinacea를 첨가하지 않은 수지상세포를 대조군으로 하여 Echinacea를 첨가한 수지상세포의 유전자 발현비가 2.5 이상으로 증가한 것들 중 면역과 관계된 유전자들은 24개였고, 실험에 사용한 수지상세포들은 모두 미성숙 수지상세포의 특징적인 표면항원들을 가지고 있음을 유세포 분석으로 확인하였다. Echinacea가 단구와 수지상세포 둘 다에서 의미있게 유전자발현비가 증가된 것들이 7개 있었는데, 이들은 CD44, IFI 30, MRC 1, CCR 7, CLK 2, syntenin, cytochrome C oxidase subunit VIII 등의 유전자들이었다. 특히 발현비가 3.5 이상으로 높은 유전자들을 그 발현비 순으로 나열하면 단구에서는 IFI 30, CLK 2, syntenin, superoxide dismutase 2 등 4개의 유전자들이 있었고, 수지상세포에서는 somatomedin A, methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A(Cys-Cys), member 22, ubiquitin-conjugating enzyme E2L 6, hexosaminidase B, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor epsilon, CCR 7 등 8개의 유전자들이 있었다. 결 론 : 본 연구는 Echinacea가 $CD14^+$ 단구 및 수지상세포에서 발현을 증가시키는 면역관련 유전자들을 cDNA microarray chip을 이용하여 검색하였고, 향후 이 유전자들을 기초로 정량적이고 기능적으로 분석할 수 있는 토대를 마련하였다.

진주담치(Mytilus edulis) 복합추출물을 이용한 진주담치소스의 제조 및 품질특성 (Processing and Quality Characteristics of Sea Mussel Mytilus edulis Sauces from Sea Mussel Complex Extract)

  • 김선근;조준현;황석민;남현규;최종덕;오광수
    • 한국수산과학회지
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    • 제50권6호
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    • pp.656-661
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    • 2017
  • To develop a highly value-added product from extract from small and damaged sea mussels Mytilus edulis, we prepared two types of sea mussel sauce (MS): bottled (BMS) and retort pouched (RMS). We investigated the processing conditions, quality metrics and flavor compounds in each type of sauce. We found that the most appropriate base formulation for both BMS and RMS consisted of 40.0% SME (Brix $30^{\circ}$), 15.0% sugar, 6.0% salt, 4.0% monosodium glutamate, 4.0% soy sauce, 3.5% starch, 3.0% yeast extract, 3.5% wheat flour and 21.0% water. The crude protein, salinity, volatile basic nitrogen and amino-nitrogen content of the BMS and RMS were 8.7% and 8.8%, 9.3% and 9.2%, 24.9 and 31.4 mg/100 g, and 468.5 and 455.1 mg/100 g, respectively. For comparison, the ranges of these values in commercial oyster sauces (COS) are 4.7-7.5%, 10.7-12.0%, 8.2-12.5 mg/100 g, and 225.7-448.2 mg/100 g, respectively. The total free amino acid content of RMS and Premium COS was 7,215.7 and 6,160.7 mg/100 g, respectively, and the main free amino acids were glutamic acid, taurine, glycine, alanine, arginine, proline and lysine. These results demonstrate that BMS and RMS have favorable organoleptic qualities and good storage stability compared to COS, and are suitable for commercialization as high-flavor seasoning sauces.

마카 품종별 조다당 획분의 대식세포 활성 (Macrophage Stimulating Activity of Crude Polysaccharide on Maca (Lepidium meyenii) Varieties)

  • 신현영;김훈;정은진;유광원
    • 한국식품영양학회지
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    • 제35권1호
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    • pp.7-15
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    • 2022
  • Maca roots (Lepidium meyenii) are an important medicinal herb that have long been used by the Andes-indigenous peoples and South Americans. In Korea, recently, it has attracted attention as a health food material because of nutritional values and physiological activities. The purpose of this study was to investigate the industrial applicability of maca (red and golden varieties; R&G) as immunostimulating materials. In the macrophage stimulating assay using RAW 264.7 cells at 125~500 ㎍/mL of non-cytotoxicity doses, G-HW showed the most potent production of TNF-α, IL-6 and nitric oxide compared to red maca or the other extracts. The general component analysis results showed that all extracts comprised more than 90% neutral sugars with small amounts of uronic acid and protein. Meanwhile, component sugar analysis showed the difference in the content of uronic acids of cold- and hot-water extract. Additionally, the further fractionation of G-HW into crude polysaccharide (G-CP) greatly enhanced the macrophage stimulating activity, and G-CP contained macromolecules over 144 kDa, comprised mainly of glucose and galacturonic acid (51.0 and 34.9%). In conclusion, crude polysaccharide from maca showed industrial applicability as immunostimulating material, and especially golden maca showed higher macrophage stimulating activity than red maca.

Genetic Variation in PDCD6 and Susceptibility to Lung Cancer

  • He, Yan-Qi;Zhou, Bin;Shi, Shao-Qing;Zhang, Lin;Li, Wei-Min
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권9호
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    • pp.4689-4693
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    • 2012
  • Lung cancer is the most common type of cancer and one of the leading causes of death in the world. Genetic factors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein 6, may function as a tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80% to newly histologically diagnosed lung cancer patients. To explore the relationship between PDCD6 and NSCLC, we examined two single nucleotide polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region) of the PDCD6gene.A hospital-based case-control study was carried out including 302 unrelated NSCLC patients and 306 healthy unrelated subjects. Significantly increased NSCLC risk was found to be associated with the T allele of rs4957014 (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of rs3756712 did not shown any significant difference between NSCLC group and controls (P=0.327, OR=0.879, 95%CI=0.679-1.137). In conclusion, we firstly demonstrated the association between the PDCD6 gene and risk of NSCLC in a Chinese Han population.

Synthesis and Biological Evaluation of Novel IM3829 (4-(2-Cyclohexylethoxy)aniline) Derivatives as Potent Radiosensitizers

  • Ahn, Jiyeon;Nam, Ky-Youb;Lee, Sae-Lo-Oom;Ryu, Hwani;Choi, Hyun Kyung;Song, Jie-Young
    • Bulletin of the Korean Chemical Society
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    • 제35권12호
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    • pp.3623-3626
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    • 2014
  • Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

Structural Characterization of pre-miRNA 155

  • Kim, Won-Je;Shin, JiYeon;Bang, Kyeongmi;Song, Hyun Kyu;Kim, Nak-Kyoon
    • 한국자기공명학회논문지
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    • 제20권2호
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    • pp.46-49
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    • 2016
  • MiRNA-155, upregulated in various cancers, is one of the miRNAs that suppress apoptosis of human cancer. Thus, inhibition of the maturation of miRNA-155 could be an effective way to induce apoptotic cancer cell death. The apical stem-loop of the pre-miRNA-155 has been known as a Dicer biding site for RNA cleavage. Here, to understand the molecular basis of the tertiary interaction between pre-miRNA-155 with Dicer, we characterize the structure of the apical stem-loop of pre-miRNA-155 using NMR spectroscopy. The RNA has a stem-bulge-stem-loop-stem structure, which is consist of G-C Watson-Crick and G-U Wobble base pairs. The assignments of imino- protons were further confirmed by 2D $^{15}N-^1H$ HSQC NMR spectrum. The NMR parameters obtained in this study can be further used to investigate the tertiary interaction between pre-miRNA-155 and other biomolecules such as protein, nucleic acids, or small chemicals which might be used to control the apoptosis of cancer.