• Title/Summary/Keyword: sRAGE protein

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Receptor for Advanced Glycation Endproducts (RAGE), Its Ligands, and Soluble RAGE: Potential Biomarkers for Diagnosis and Therapeutic Targets for Human Renal Diseases

  • Lee, Eun Ji;Park, Jong Hoon
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.224-229
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    • 2013
  • Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that is able to bind several different ligands, including advanced glycation endproducts, high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-${\beta}$-protein, Mac-1, and phosphatidylserine. Its interaction is engaged in critical cellular processes, such as inflammation, proliferation, apoptosis, autophagy, and migration, and dysregulation of RAGE and its ligands leads to the development of numerous human diseases. In this review, we summarize the signaling pathways regulated by RAGE and its ligands identified up to date and demonstrate the effects of hyper-activation of RAGE signals on human diseases, focused mainly on renal disorders. Finally, we propose that RAGE and its ligands are the potential targets for the diagnosis, monitoring, and treatment of numerous renal diseases.

Co-Culture Model Using THP-1 Cell and HUVEC on AGEs-Induced Expression of Cytokines and RAGE (THP-1 Cell과 HUVEC을 이용한 Co-Culture Model System에서 최종당화산물에 의한 Cytokines와 RAGE 발현)

  • Lee, Kwang-Won;Lee, Hyun-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.3
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    • pp.385-392
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    • 2011
  • Although monoculture methods have been remarkably useful due to their simplicity, they have serious limitation because of the different types of cells communication with each other in many physiological situations. We demonstrated levels of markers of endothelial dysfunction such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$) as well as stimulation of receptor of advanced glycation endproducts (AGEs) on monoand co-culture system such as only monocyte (THP-1) cultivation system, only endothelial cell (HUVEC) cultivation system, and co-cultivation system of THP-1 and HUVEC. The mRNA levels of TNF-$\alpha$ and IL-1$\beta$ on HUVEC increased by the co-culture with monocyte after 4 hr at 100 ${\mu}g/mL$ glyceraldehyde-AGE. The secreted protein contents into medium of TNF-$\alpha$ and IL-1$\beta$ increased after 8 hr approximately 2~2.5 times compared to mono-cultivation. In contrast, the mRNA level of receptor of AGE (RAGE) was relatively insensitive on the co-culture system. The mediators by which monocytes activate endothelial cell have not been fully elucidated. In this study we confirmed production of soluble cytokines such as TNF-$\alpha$ and IL-1$\beta$ by monocytes. Use of monocyte conditioned medium, which contains both cytokines, can activate endothelial cell.

A Study on Dietary Related Factors and Blood Parameters of Obese Children Residing in Samcheok (삼척지역 일부 중등도 이상 비만 아동의 식생활관련 요인과 혈액성상에 관한 연구)

  • Lee, Jae-Cheol;Kim, Mi-Hyeon
    • Journal of the Korean Dietetic Association
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    • v.11 no.2
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    • pp.190-204
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    • 2005
  • The purpose of this study was to investigate the dietary related factors and blood parameters of moderately or severely obese children residing in Samcheok. Anthropometric measurement, 24-hour recall for dietary intake, blood analysis and questionnaire response including nutritional knowledge, nutritional attitude, body image recognition and eating habits were conducted in 23 obese children(16 boys and 7 girls) and their mother. The mean age of subjects are 10.0 years. The average body weight, BMI, obesity index and percent body fat were 57.5㎏, 27.0㎏/$m^2$, 47.3 and 38.1% in boys and 51.0㎏, 24.8㎏/$m^2$, 40.3 and 43.9% in girls. The average nutritional attitude, the self-satisfaction and the nutritional knowledge scores in subjects were 29.9/40, 32.7/50 and 7.3/10, respectively. 34.8% of the subjects were unsatisfied with their body image, whereas, 81.8% of their mothers were unsatisfied with children’s body image. 60.9% of subjects had one or both obese parents. Average intake of energy were 90.6% of RDA in boys and 84.3% of RDA in girls. The ratio of energy from carbohydrate/protein/fat were 66/16/18 in boys and 66/17/17 in girls. The mean serum cholesterol concentration of the subjects was 191.8mg/dl and 78.3% of the subjects were above the normal serum cholesterol rage of children. In the results of correlation analysis, obesity index was negatively correlated with self and mother’s nutritional attitude scores. Body weight and BMI were positively correlated with vitamin C(p<0.05) and fruits(p<0.05) intakes. And there was a positive correlation between obesity index and BMI, and serum cholesterol(p<0.05).

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HMGB1 Switches Alkylating DNA Damage-Induced Apoptosis to Necrosis (HMGB1에 의한 alkylating DNA 손상에 의해 유도된 세포사멸의 세포괴사로의 전환)

  • Lee, Su-Yeon;Jeong, Eui-Kyong;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Cho-Hee;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.21 no.7
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    • pp.953-960
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    • 2011
  • Necrosis is characterized by the cell membrane rupture and release of the cellular contents, including high-mobility group box 1 protein (HMGB1), into the extracellular microenvironment. HMGB1 acts as a transcriptional regulator in nuclei, but exerts a pro-inflammatory and tumor-promoting cytokine activity when released into the extracellular space. Its overexpression is associated with tumor progression and chemoresistance. Thus, HMGB1 acts as a clinically important molecule in tumor biology. In this study, we examined whether HMGB1 affects cell death induced by anti-cancer drugs. Here we show that HMGB1 prevented cisplatin (alkylating agent)-induced apoptosis and switched the cell fate to necrosis in MCF-7, MDA-MB231, and MDA-MB361 cells. Similar apoptosis-to-necrosis switch effects of HMGB1 were observed in cells treated with 4-HC, another alkylating agent. In contrast, HMGB1 did not exert any significant effects on docetaxel (DOC)-induced apoptosis in MCF-7 cells. We also show that cisplatin-induced apoptosis was switched to necrosis in MCF-7 multicellular tumor spheroids (MTS) that were cultured for 8 days and had necrotic cores, but DOC-induced apoptosis was prevented without the apoptosis-to-necrosis switch. Finally, the levels of RAGE, a receptor of HMGB1, were increased with extended culture of MTS. These findings demonstrate that HMGB1 switches alkylating agent-induced apoptosis to necrosis, suggesting that the strategy to prevent necrosis occurring as an undesirable action of alkylating agent-based chemotherapy should be delineated to improve the efficacy of chemotherapy for cancer.

Quality Changes of Dried Lavers during Processing and Storage 3. Changes in Pigments, Trypsin Indigestible Substrates(TIS) and Dietary Fiber Content during Roasting and Storage (김의 가공 및 저장중의 품질변화 3. 배소 및 저장중의 색소, Trypsin 저해물질(TIS) 및 Dietary Fiber의 변화)

  • LEE Kang-Ho;RYUK Ji-Hee;JEONG In-Hak;JUNG Woo-Jin
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.23 no.4
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    • pp.280-288
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    • 1990
  • Quality stability of dried lavers during roasting and storage was investigated by measuring the changes of pigment contents including chlorophyll a, carotenoids and biliproteins, the content of trypsin indigestible substrates(TIS), in vitro apparent protein digestibility, and dietary fiber. In heat treatment or roasting of dried laver, carotenoids and chlorophyll a were found to be more stable than biliproteins. Chlorophyll a and carotenoids were retained more than $85\%$ during roasting for 1 hour at $120^{\circ}C$ while biliproteins were retained only $10\%$ at the same temperature. The in vitro digestility of dried layers tended to increase with raising the roasting temperature. The in vitro digestibility of $85\%$ for the roasted laver at $100^{\circ}C$ was higher than that observed in the control of $80\%$. There was a correlation between the decrease in TIS and biliproteins as the laver was roasted. The soulble dietary fiber(SDF) content was substantially increased by heat treatment. The extent of protein digestiblility appeared to be related to the increase of SDF content. In the storage of roasted lavers under both water activities 0.1 and 0.65, the loss of the pigments and TlS were markedly retarded at Aw 0.1. Chlorophyll a was retained about $20\%$ at aw 0.65 and $75\%$ at aw 0.1 after 20 week sto-rage. At worst, more than $90\%$ of the carotenoids were lost at aw 0.65 after 20 week, while biliproteins were comparatively stable at the same water activity. TIS decreased about $15\%$ and in vitro apparent protein digestibility increased up to $92\%$ at aw 0.65 during storage.

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Effect of Moutan Cortex Radicis on gene expression profile of differentiated PC12 rat cells oxidative-stressed with hydrogen peroxide (모단피의 PC12 cell 산화억제 효과 및 neuronal 유전자 발현 profile 분석에 대한 연구)

  • Kim Hyun Hee;Rho Sam Woong;Na Youn Gin;Bae Hyun Su;Shin Min Kyu;Kim Chung Suk;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.529-541
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    • 2003
  • Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.