Altered gene and protein expression in liver of the obese spontaneously hypertensive/NDmcr-cp rat.
Altered gene and protein expression in liver of the obese spontaneously hypertensive/NDmcr-cp rat.
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DOI：
10.1186/1743-7075-9-87
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发表时间：
2012-09-21
影响因子：
4.5
通讯作者：
Ichihara S
中科院分区：
文献类型：
--
作者：
Chang J;Oikawa S;Ichihara G;Nanpei Y;Hotta Y;Yamada Y;Tada-Oikawa S;Iwahashi H;Kitagawa E;Takeuchi I;Yuda M;Ichihara S
由于遗传背景和生活方式的异质性，研究人类代谢综合征的机制很困难。本研究调查了代谢综合征动物模型中基因和蛋白质谱的变化，以确定与代谢综合征相关的肥胖发病机制和进展相关的分子靶标。我们从 6 周和 25 周龄自发性高血压/NIH 肥胖大鼠 SHR/NDmcr-cp (CP)、SHR/Lean (Lean) 和 Wistar京都大鼠 (WKY) 的肝组织中提取 mRNA 和蛋白质，并进行微阵列分析和与基质辅助激光解吸相关的二维差异凝胶电泳 (2D-DIGE) 电离飞行时间串联质谱 (MALDI-TOF/TOF MS)。与WKY和Lean相比，微阵列分析确定了6周龄和25周龄CP中25个显着上调基因（P < 0.01；log10 > 1）和31个显着下调基因（P < 0.01；log10 < −1）。已知其中一些基因参与重要的生物过程，例如电子转运蛋白活性、电子转运、脂质代谢、离子转运、转移酶和离子通道活性。 MALDI-TOF/TOF MS 鉴定出 6 周龄和 25 周龄 CP 中的 31 种蛋白质与年龄匹配的 WKY 和 Lean 相比有 ±1.2 倍变化 (P < 0.05)。上调的蛋白参与代谢过程、生物调节、催化活性和结合，而下调的蛋白参与内质网应激相关的未折叠蛋白反应。在转录组分析中表达发生显着变化的基因与蛋白质组分析中鉴定出的蛋白质极少相匹配。然而，带注释的功能分类可能为了解与代谢综合征相关的肥胖发病机制提供重要的参考资源。
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. 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). 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. 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.