...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular & cellular proteomics: MCP >The nutrigenetics of hyperhomocysteinemia: quantitative proteomics reveals differences in the methionine cycle enzymes of gene-induced versus diet-induced hyperhomocysteinemia.
【24h】

The nutrigenetics of hyperhomocysteinemia: quantitative proteomics reveals differences in the methionine cycle enzymes of gene-induced versus diet-induced hyperhomocysteinemia.

机译：高同型半胱氨酸血症的营养学：定量蛋白质组学揭示了基因诱导的高半胱氨酸血症与饮食引起的高同型半胱氨酸血症的蛋氨酸循环酶之间的差异。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Hyperhomocysteinemia has long been associated with atherosclerosis and thrombosis and is an independent risk factor for cardiovascular disease. Its causes include both genetic and environmental factors. Although homocysteine is produced in every cell as an intermediate of the methionine cycle, the liver contributes the major portion found in circulation, and fatty liver is a common finding in homocystinuric patients. To understand the spectrum of proteins and associated pathways affected by hyperhomocysteinemia, we analyzed the mouse liver proteome of gene-induced (cystathionine beta-synthase (CBS)) and diet-induced (high methionine) hyperhomocysteinemic mice using two-dimensional difference gel electrophoresis and Ingenuity Pathway Analysis. Nine proteins were identified whose expression was significantly changed by 2-fold (p < or = 0.05) as a result of genotype, 27 proteins were changed as a result of diet, and 14 proteins were changed in response to genotype and diet. Importantly, three enzymes of the methionine cycle were up-regulated. S-Adenosylhomocysteine hydrolase increased in response to genotype and/or diet, whereas glycine N-methyltransferase and betaine-homocysteine methyltransferase only increased in response to diet. The antioxidant proteins peroxiredoxins 1 and 2 increased in wild-type mice fed the high methionine diet but not in the CBS mutants, suggesting a dysregulation in the antioxidant capacity of those animals. Furthermore, thioredoxin 1 decreased in both wild-type and CBS mutants on the diet but not in the mutants fed a control diet. Several urea cycle proteins increased in both diet groups; however, arginase 1 decreased in the CBS(+/-) mice fed the control diet. Pathway analysis identified the retinoid X receptor signaling pathway as the top ranked network associated with the CBS(+/-) genotype, whereas xenobiotic metabolism and the NRF2-mediated oxidative stress response were associated with the high methionine diet. Our results show that hyperhomocysteinemia, whether caused by a genetic mutation or diet, alters the abundance of several liver proteins involved in homocysteine/methionine metabolism, the urea cycle, and antioxidant defense.
机译：高同型半胱氨酸血症长期以来与动脉粥样硬化和血栓形成有关，是心血管疾病的独立危险因素。其原因包括遗传和环境因素。尽管高半胱氨酸作为蛋氨酸循环的中间产物在每个细胞中产生，但肝脏是循环中发现的主要部分，而脂肪肝是高胱氨酸尿症患者的常见发现。为了了解受高同型半胱氨酸血症影响的蛋白质谱图和相关途径，我们使用二维差异凝胶电泳法分析了小鼠基因诱导的（胱硫醚β合酶）和饮食诱导的（高蛋氨酸）高同型半胱氨酸血症小鼠的肝蛋白质组。独创性途径分析。鉴定出9种蛋白质，其表达因基因型而显着改变了2倍（p <或= 0.05），饮食使27种蛋白质发生了改变，而14种蛋白质因基因型和饮食而发生了变化。重要的是，蛋氨酸循环的三种酶被上调。 S-腺苷同型半胱氨酸水解酶响应基因型和/或饮食而增加，而甘氨酸N-甲基转移酶和甜菜碱-同型半胱氨酸甲基转移酶仅响应饮食而增加。在高蛋氨酸饮食的野生型小鼠中，抗氧化剂蛋白过氧化物酶1和2增加，但CBS突变体中没有，表明这些动物的抗氧化能力失调。此外，饮食中的野生型和CBS突变体中的硫氧还蛋白1均下降，但饲喂对照饮食的突变体中硫氧还蛋白1却没有下降。在两个饮食组中，几种尿素循环蛋白都增加了。但是，在饲喂对照饮食的CBS（+/-）小鼠中精氨酸酶1减少。途径分析确定类视黄醇X受体信号通路是与CBS（+/-）基因型相关的排名最高的网络，而异生物素代谢和NRF2介导的氧化应激反应与高蛋氨酸饮食相关。我们的结果表明，高半胱氨酸血症，无论是由基因突变还是饮食引起的，都会改变参与高半胱氨酸/蛋氨酸代谢，尿素循环和抗氧化剂防御作用的几种肝脏蛋白质的丰度。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号