期刊论文详细信息
Nutrition & Metabolism
Altered gene and protein expression in liver of the obese spontaneously hypertensive/NDmcr-cp rat
Sahoko Ichihara4  Masao Yuda8  Ichiro Takeuchi7  Emiko Kitagawa1  Hitoshi Iwahashi6  Saeko Tada-Oikawa2  Yoshiji Yamada4  Yasuhiro Hotta4  Yui Nanpei4  Gaku Ichihara3  Shinji Oikawa5  Jie Chang3 
[1] Applied Science, Roche Diagnostics, Tokyo, Japan;Graduate School of Regional Innovation Studies, Mie University, 1577 Kurimamachiya-cho, Tsu 514-8507, Japan;Department of Environmental and Occupational Health, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan;Department of Molecular and Environmental Medicine, Mie University Graduate School of Medicine, Tsu, Japan;Graduate School of Applied Biological Sciences, Gifu University, Gifu, Japan;Department of Engineering, Nagoya Institute of Technology, Nagoya, Japan;Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Japan
关键词: Liver;    Obesity;    Proteomics analysis;    Microarray analysis;    Pathophysiology;    Metabolic syndrome;   
Others  :  811974
DOI  :  10.1186/1743-7075-9-87
 received in 2012-04-24, accepted in 2012-09-07,  发布年份 2012
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【 摘 要 】

Background

It is difficult to study the mechanisms of the metabolic syndrome in humans due to the heterogeneous genetic background and lifestyle. The present study investigated changes in the gene and protein profiles in an animal model of the metabolic syndrome to identify the molecular targets associated with the pathogenesis and progression of obesity related to the metabolic syndrome.

Methods

We extracted mRNAs and proteins from the liver tissues of 6- and 25-week-old spontaneously hypertensive/NIH –corpulent rat SHR/NDmcr-cp (CP), SHR/Lean (Lean) and Wistar Kyoto rats (WKY) and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS).

Results

The microarray analysis identified 25 significantly up-regulated genes (P < 0.01; log10 > 1) and 31 significantly down-regulated genes (P < 0.01; log10 < −1) in 6- and 25-week-old CP compared with WKY and Lean. Several of these genes are known to be involved in important biological processes such as electron transporter activity, electron transport, lipid metabolism, ion transport, transferase, and ion channel activity. MALDI-TOF/TOF MS identified 31 proteins with ±1.2 fold change (P < 0.05) in 6- and 25-week-old CP, compared with age-matched WKY and Lean. The up-regulated proteins are involved in metabolic processes, biological regulation, catalytic activity, and binding, while the down-regulated proteins are involved in endoplasmic reticulum stress-related unfolded protein response.

Conclusion

Genes with significant changes in their expression in transcriptomic analysis matched very few of the proteins identified in proteomics analysis. However, annotated functional classifications might provide an important reference resource to understand the pathogenesis of obesity associated with the metabolic syndrome.

【 授权许可】

   
2012 Chang et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Fall CH, Borja JB, Osmond C, Richter L, Bhargava SK, Martorell R, Stein AD, Barros FC, Victora CG, COHORTS group: Infant-feeding patterns and cardiovascular risk factors in young adulthood: data from five cohorts in low- and middle-income countries. Int J Epidemiol 2011, 40:47-62.
  • [2]Arnlöv J, Ingelsson E, Sundström J, Lind L: Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 2010, 121:392-400.
  • [3]Rosato V, Zucchetto A, Bosetti C, Dal Maso L, Montella M, Pelucchi C, Negri E, Franceschi S, La Vecchia C: Metabolic syndrome and endometrial cancer risk. Ann Oncol 2011, 22:884-889.
  • [4]Hsieh SD, Muto T, Tsuji H, Arase Y, Murase T: Clustering of other metabolic risk factors in subjects with metabolic syndrome. Metabolism 2010, 59:697-702.
  • [5]Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y: Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genet 2008, 45:22-28.
  • [6]Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB: The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2003, 163:427-436.
  • [7]Striffler JS, Bhathena SJ, Michaelis OE 4th, Campbell JD, Hansen CT, Scalbert E, Thibault N, Velasquez MT: Long-term effects of perindopril on metabolic parameters and the heart in the spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes mellitus and hypertension. Metabolism 1998, 47:1199-1204.
  • [8]Koletsky S: Obese spontaneously hypertensive rats-a model for study of atherosclerosis. Exp Mol Pathol 1973, 19:53-60.
  • [9]Yamamoto J, Ikena K, Yamori Y: Obese and hypertensive SHR/NDmcr-cp rats -A model of metabolic syndrome. Adiposcience 2005, 2:243-248.
  • [10]Ichihara S, Noda A, Nagata K, Obata K, Xu J, Ichihara G, Oikawa S, Kawanishi S, Yamada Y, Yokota M: Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure. Cardiovasc Res 2006, 69:726-735.
  • [11]Nishizawa T, Iwase M, Kanazawa H, Ichihara S, Ichihara G, Nagata K, Obata K, Kitaichi K, Yokoi T, Watanabe M, Tsunematsu T, Ishikawa Y, Murohara T, Yokota M: Serial Alteration of β-adrenergic signaling in dilated cardiomyopathic hamsters. Circ J 2004, 68:1051-1060.
  • [12]Kondo T, Hirohashi S: Application of highly sensitive fluorescent dyes (CyDye DIGE Fluor saturation dyes) to laser microdissection and two-dimensional difference gel electrophoresis (2D-DIGE) for cancer proteomics. Nat Protoc 2006, 1:2940-2056.
  • [13]Oikawa S, Yamada T, Minohata T, Kobayashi H, Furukawa A, Tada-Oikawa S, Hiraku Y, Murata M, Kikuchi M, Yamashima T: Proteomic identification of carbonylated proteins in the monkey hippocampus after ischemia-reperfusion. Free Radic Biol Med 2009, 46:1472-1477.
  • [14]Furukawa A, Oikawa S, Hasegawa-Ishii S, Chiba Y, Kawamura N, Takei S, Yoshikawa K, Hosokawa M, Kawanishi S, Shimada A: Proteomic analysis of aging brain in SAMP10 mouse: a model of age-related cerebral degeneration. Mech Ageing Dev 2010, 131:379-388.
  • [15]Huang Z, Ichihara S, Oikawa S, Chang J, Zhang L, Takahashi M, Subramanian K, Mohideen SS, Wang Y, Ichihara G: Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane. Toxicol Appl Pharmacol 2011, 257:93-101.
  • [16]Iwahashi H, Kitagawa E, Suzuki Y, Ueda Y, Ishizawa YH, Nobumasa H, Kuboki Y, Hosoda H, Iwahashi Y: Evaluation of toxicity of the mycotoxin citrinin using yeast ORF DNA microarray and Oligo DNA microarray. BMC Genomics 2007, 8:95. BioMed Central Full Text
  • [17]Iwahashi Y, Kitagawa E, Iwahashi H: Analysis of mechanisms of T-2 toxin toxicity using yeast DNA microarrays. Int J Mol Sci 2008, 9:2585-2600.
  • [18]Relógio A, Schwager C, Richter A, Ansorge W, Valcárcel J: Optimization of oligonucleotide-based DNA microarrays. Nucleic Acids Res 2002, 30:e51.
  • [19]Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer DP, Takami Y, Nakayama T, Suiko M, Liu M-C: Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem 1998, 273:33929-33935.
  • [20]Khor VK, Dhir RD, Yin X, Ahima RS, Song W-C: Estrogen sulfotransferase regulates body fat and glucose homeostasis. Am J Physiol Endocrinol Metab 2010, 299:E657-E664.
  • [21]Ahima RS, Stanley TL, Khor VK, Zanni MV, Grinspoon SK: Estrogen sulfotransferase is expressed in subcutaneous adipose tissue of obese humans in associated with TNF-α and SOCS3. J Clin Endocrinol Metab 2011, 96:E1153-E1158.
  • [22]Freimuth RR, Raftogianis RB, Wood TC, Moon E, Kim U-J, Xu J, Siciliano MJ, Weinshilboum RM: Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization. Genomics 2000, 65:157-165.
  • [23]Buqué X, Martínez MJ, Cano A, Miquilena-Colina ME, García-Monzón C, Aspichueta P, Ochoa B: A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats. J Lipid Res 2010, 51:500-513.
  • [24]Kislinger T, Cox B, Kannan A, Chung C, Hu P, Ignatchenko A, Scott MS, Gramolini AO, Morris Q, Hallett MT, Rossant J, Hughes TR, Frey B, Emili A: Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell 2006, 125:173-186.
  • [25]Hornshøj H, Bendixen E, Conley LN, Andersen PK, Hedegaard J, Panitz F, Bendixen C: Transcriptomic and proteomic profiling of two porcine tissues using high-throughput technologies. BMC Genomics 2009, 10:30. BioMed Central Full Text
  • [26]Rogers S, Girolami M, Kolch W, Waters KM, Liu T, Thrall B, Wiley HS: Investigating the correspondence between transcriptomic and proteomic expression profiles using coupled cluster models. Bioinformatics 2008, 24:2894-2900.
  • [27]Qiu Y, Marek M: Transcriptional control of the calreticulin gene in health and disease. Int J Biochem Cell Biol 2009, 41:531-538.
  • [28]Ferreira V, Molina MC, Valck C, Rojas A, Aguilar L, Ramírez G, Schwaeble W, Ferreira A: Role of calreticulin from parasites in its interaction with vertebrate hosts. Mol Immun 2004, 40:1279-1291.
  • [29]Szabo E, Feng T, Dziak E, Opas M: Cell adhesion and spreading affect adipogenesis from embryonic stem cells. The role of calreticulin. Stem Cells 2009, 27:2092-2102.
  • [30]Lozyk MD, Papp S, Zhang X, Nakamura K, Michalak M, Opas M: Ultrastructural analysis of development of myocardium in calreticulin-deficient mice. BMC Dev Biol 2006, 6:54. BioMed Central Full Text
  • [31]Bass J, Chiu G, Argon Y, Steiner DF: Folding of insulin receptor monomers is facilitated by the molecular chaperones calnexin and calreticulin and impaired by rapid dimerization. J Cell Biol 1998, 141:637-646.
  • [32]Jain HT, Many TN, Riahi Y, Kaiser N, Eckel J, Sasson S: Calreticulin destabilizes glucose transporter-1 mRNA in vascular endothelial and smooth muscle cells under high-glucose conditions. Cir Res 2005, 97:1001-1008.
  • [33]Jalali S, Aghasi M, Yeganeh B, Mesaeli N: Calreticulin regulates insulin receptor expression and its downstream PI3 Kinase/Akt signalling pathway. Biochim Biophy Acta 2008, 1783:2344-2351.
  • [34]Hatahet F, Ruddock LW: Substrate recognition by the protein disulfide isomerases. FEBS J 2007, 274:5223-5234.
  • [35]Puig A, Gilbert HF: Protein disulfide isomerase exhibits chaperone and anti-chaperone activity in the oxidative refolding of lysozyme. J Biol Chem 1994, 269:7764-7771.
  • [36]Jessop CE, Chakravarthi S, Garbi N, Hämmerling GJ, Lovell S, Bulleid NJ: ERp57 is essential for efficient folding of glycoproteins sharing common structural domains. EMBO J 2007, 26:28-40.
  • [37]Rutkevich LA, Cohen-Doyle MF, Brockmeier U, Williams DB: Functional relationship between protein disulfide isomerase family members during the oxidative folding of human secretory proteins. Mol Biol Cell 2010, 21:3093-3105.
  • [38]Boden G, Song W, Duan X, Cheung P, Kresge K, Barrero C, Merali S: Infusion of glucose and lipids at physiological rates causes acute endoplasmic reticulum stress in rat liver. Obesity 2011, 19:1366-1373.
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