• 제목/요약/키워드: liver proteome

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Development of Proteomics and Applications of Proteomics in Toxicology

  • Jung, Woon-Won;Huh, Yoon-Ee;Ryu, Jae-Chun;Lee, Eun-Il;Sul, Dong-Geun
    • Molecular & Cellular Toxicology
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    • 제1권1호
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    • pp.7-12
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    • 2005
  • Proteomics has recently received intense scientific interest after the completion of the Human Genome Project, because this genome-based high technology allows to search new drug targets or diagnostic markers. Many proteome projects including Human plasma proteome projects (HPPP), Human liver proteome projects (HLPP), Human brain proteome projects (HBPP), and Mouse and Rat Proteome Project (MRPP) have been carried out and proteomic analytical techniques have been developed in second dimensional electrophoresis (2-DE) and LC/MS system. This powerful method has been applied in toxicology producing a new term "Toxicoproteomics". In this review, recent proteome projects, proteomic technologies, and toxicoproteomics will be discussed.

Time-Dependent Hepatic Proteome Analysis in Lean and Diet-Induced Obese Mice

  • Oh, Tae-Seok;Kwon, Eun-Young;Choi, Jung-Won;Choi, Myung-Sook;Yun, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • 제21권12호
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    • pp.1211-1227
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    • 2011
  • C57BL/6J mice have been widely used as a diet-induced obesity model because they trigger common features of the human metabolic syndrome. In the present study, C57BL/6J male mice were fed either a high-fat diet (HFD) or normal diet (ND) during a 24-week period, and then the age-dependent liver proteome of mice in two groups was analyzed using 2-DE combined with MALDI-TOF-MS. Among identified proteins, up-regulated proteins were subdivided to early (during the first 4 weeks) and late (20~24 weeks) markers that played a role in diet-induced obesity development. Important early markers included ketohexokinase and prohibitin, and late markers included the 75 kDa glucose-regulated protein, citrate synthase, and selenium-binding liver protein. Of these, the 75 kDa glucosere-gulated protein has already been linked to obesity; however, prohibitin protein involved in obesity was identified for the first time in this study. In order to validate the proteomic results and gain insight into metabolic changes between the two groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combined results of proteomic analysis with Western blot analysis revealed that antioxidant enzymes were progressively decreased, whereas cytoskeletal proteins were time-dependently increased in HFD mice.

Identification of Differentially Expressed Proteins in Liver in Response to Subacute Ruminal Acidosis (SARA) Induced by High-concentrate Diet

  • Jiang, X.Y.;Ni, Y.D.;Zhang, S.K.;Zhang, Y.S.;Shen, X.Z.
    • Asian-Australasian Journal of Animal Sciences
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    • 제27권8호
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    • pp.1181-1188
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    • 2014
  • The aim of this study was to evaluate protein expression patterns of liver in response to subacute ruminal acidosis (SARA) induced by high-concentrate diet. Sixteen healthy mid-lactating goats were randomly divided into 2 groups and fed either a high-forage (HF) diet or a high-concentrate (HC) diet. The HC diet was expected to induce SARA. After ensuring the occurrence of SARA, liver samples were collected. Proteome analysis with differential in gel electrophoresis technology revealed that, 15 proteins were significantly modulated in liver in a comparison between HF and HC-fed goats. These proteins were found mainly associated with metabolism and energy transfer after identified by matrix-assisted laser desorption ionization/time of flight. The results indicated that glucose, lipid and protein catabolism could be enhanced when SARA occurred. It prompted that glucose, lipid and amine acid in the liver mainly participated in oxidation and energy supply when SARA occurred, which possibly consumed more precursors involved in milk protein and milk fat synthesis. These results suggest new candidate proteins that may contribute to a better understanding of the mechanisms that mediate liver adaptation to SARA.

인진청간탕(茵蔯淸肝湯)이 DMN에 의한 간손상 proteome에 미치는 영향 (The Effects of Injinchunggan-tang (Yinchenchinggan-tang) on DMN Liver Damage from Applying Proteomics)

  • 김효진;김영철;이장훈;우홍정
    • 대한한방내과학회지
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    • 제28권1호
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    • pp.133-148
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    • 2007
  • Objectives : The purpose of our study was to investigate the effects of Injinchunggan-tang (Yinchenchinggan-tang) on DMN liver damage caused by applying proteomics. Materials and Methods: Sprague-Dawley rats were used in this experiment; the rats were divided into the normal group (normal saline), the control group (DMN) and the samplegroup (DMN+IJCGT). The DMN was induced 3 days a week for 3 weeks in the control group. The normal saline without DMN was induced by the same method in the normal group. Injinchunggan-tang extract was orally administered twice a day for 3 weeks after DMN was induced in the sample group. The livers of each group were processed and we investigated histology, OxyBlot, 2-dimensional electrophoresis, and western blot of liver of each group. Results : In the histological findings of the liver, the control group showed portal fibrosis with a few septa or without septa. The sample group showed no fibrosis or portal fibrosis without septa. In the OxyBlot finding, Injinchunggan-tang prevented liver damage by oxidation. In the 2-dimensional electrophoresis finding, formiminotransferase cyclodeaminase (FTCD), FYVE-finger containing protein, aldehyde dehydrogenase (ALDH), and ratio of predicted : hypothetical protein LOC68668 isoform 1 were changed. Conclusions : Injinchunggan-tang exerts an inhibitory effect against the fibrosis and oxidation induced by the DMN in the rat liver cell, and some proteins induced by the DMN were changed by Injinchunggan-tang.

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청간해주탕(淸肝解酒湯)이 알코올성 간손상 Proteome에 미치는 영향 (The Effects of Chungganhaeju-tang (Qingganjiejiu-tang) on Alcoholic Liver Damages by Applying Proteomics)

  • 정윤종;김영철;우홍정;이장훈
    • 대한한방내과학회지
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    • 제28권1호
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    • pp.68-79
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    • 2007
  • Objectives : The purpose of our study was to investigate the effects of Chungganhaeju-tang (Qingganjiejiu-tang) on alcoholic liver damage by applying proteomics. Materials and Methods : Sprague-Dawley rats were used in this experiment; the rats were divided into a control group, alcohol group and Chungganhaeju-tang + alcohol group. Ethanol was orally administered twice a day for 4 weeks to the alcohol group. Water without ethanol was administered twice a day for 4 weeks to the control group. Ethanol + Chungganhaeju-tang extract was orally administered twice a day for 4 weeks to the Chungganhaeju-tang + alcohol group. The livers of each group were processed and we investigated histology, OxyBlot, 2-dimensional electrophoresis, and western blot of liver of each group. Results : In the histological findings of the liver, the alcohol group showed portal fibrosis with a few septa or without septa. The Chungganhaeju-tang + alcohol group showed no fibrosis or portalfibrosis without septa. In the OxyBlot finding, Chungganhaeju-tangprevented liver damage by oxidation. In the 2-dimensional electrophoresis finding, formiminotransferase cyclodeaminase (FTCD), glucose regulated protein, 58 kDa (GRP58K), aryl sulfotransferase, sulfotransferase family 1A, member 2, similar to acyl-coenzyme A oxidase-like, and catalase were changed. Conclusion : Chungganhaeju-tangexerts an inhibitory effect against the fibrosis and oxidation induced by alcohol in rat liver cell, and some proteins induced by alcohol were changed by Chungganhaeju-tang.

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Hepatotoxic mechanism of diclofenac sodium on broiler chicken revealed by iTRAQ-based proteomics analysis

  • Sun, Chuanxi;Zhu, Tianyi;Zhu, Yuwei;Li, Bing;Zhang, Jiaming;Liu, Yixin;Juan, Changning;Yang, Shifa;Zhao, Zengcheng;Wan, Renzhong;Lin, Shuqian;Yin, Bin
    • Journal of Veterinary Science
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    • 제23권4호
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    • pp.56.1-56.17
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    • 2022
  • Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10). DFS was administered orally at 10mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were "protein processing in endoplasmic reticulum," "retinol metabolism," and "glycine, serine, and threonine metabolism." Conclusions: The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Proteomic Analysis in ob/ob Mice Before and After Hypoglycemic Polysaccharide Treatments

  • Kim, Sang-Woo;Hwang, Hye-Jin;Baek, Yu-Mi;Hwang, Hee-Sun;Yun, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • 제19권10호
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    • pp.1109-1121
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    • 2009
  • In an attempt to discover novel biomarker proteins in type 2 diabetes prognosis, we investigated the influence of hypoglycemic extracellular polysaccharides (EPS) obtained from the macrofungus Tremella fuciformis on the differential levels of plasma proteins in ob/ob mice using two-dimensional gel electrophoresis (2-DE). The 2-DE analysis demonstrated that 92 spots from about 900 visualized spots were differentially regulated, of which 40 spots were identified as principal diabetes-associated proteins. By comparing control with EPS-fed mice, we found that at least six proteins were significantly altered in ob/ob mice, including Apo A-I, IV, C-III, E, retinol-binding protein 4, and transferrin, and their levels were interestingly normalized after EPS treatment. Western blot analysis revealed that the altered levels of the two regulatory molecules highlighted in diabetes and obesity (e.g., resistin and adiponectin) were also normalized in response to EPS. The Mouse Diabetes PCR Array profiles showed that the expression of 84 genes related to the onset, development, and progression of diabetes were significantly downregulated in liver, adipocyte, and muscle of ob/ob mice. EPS might act as a potent regulator of gene expression for a wide variety of genes in ob/ob mice, particularly in obesity, insulin resistance, and complications from diabetes mellitus.

단백체 분석을 위한 일차원 및 이차원 역상크로마토그래피의 비교 (Comparison of 2-D RP-RP MS/MS with 1-D RP MS/MS for Proteomic Analysis)

  • 문평곤;조영은;백문창
    • 약학회지
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    • 제54권5호
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    • pp.377-386
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    • 2010
  • Single-dimensional (1-D) and two-dimensional (2-D) LC methods were utilized to separate peptides from various sources followed by MS/MS analysis. Two-dimensional ultra-high performance liquid chromatography is a useful tool for proteome analysis, providing a greater peak capacity than 1-D LC. The most popular 2-D LC approach used today for proteomic research combines strong cation exchange and reversed-phase LC. We have evaluated an alternative mode for 2-D LC of peptides using 2-D RP-RP nano UPLC Q-TOF Mass Spectrometry, employing reversed-phase columns in both separation dimensions. As control experiments, we identified 129 proteins in 1-D LC and 322 proteins in 2-D LC from E. coli extract peptides. Furthermore, we applied this method to rat primary hepatocyte and a total of 170 proteins were identified from 1-D LC, and 527 proteins were identified from all 2-D LC system. The in-depth protein profiling established by this 2-D LC MS/MS from rat primary hepatocyte could be a very useful reference for future applications in regards to drug induced liver toxicity.