Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs
Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs
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宫内生长受限影响新生猪小肠、肝脏和骨骼肌的蛋白质组
DOI：
10.1093/jn/138.1.60
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Wu, Guoyao
中科院分区：
文献类型：
--
作者：
Wang, Junjun;Chen, Lixiang;Wu, Guoyao
正常出生体重的新生儿营养利用效率高，但宫内生长受限（IUGR）的新生儿营养利用效率降低。然而，其潜在的机制在很大程度上是未知的。本研究采用仔猪模型和蛋白质组学技术来验证IUGR影响调节小肠、肝脏和肌肉生长发育的关键蛋白质表达的假设，小肠、肝脏和肌肉是参与膳食营养素消化、吸收和代谢的主要器官。从出生时的IUGR和正常出生体重的仔猪中获得空肠、肝脏和腓肠肌，用于使用二维PAGE MS技术分析蛋白质组。结果表明，IUGR降低了调节免疫功能的蛋白质水平（免疫球蛋白和膜联蛋白A1），氧化防御（过氧化物氧还蛋白1、转铁蛋白和zeta-晶状体蛋白），中间代谢（肌酸激酶、醇脱氢酶、L-乳酸脱氢酶、前列腺素F合酶、载脂蛋白A1、儿茶酚O-甲基转移酶和磷酸甘油酸激酶1）、蛋白质合成（真核翻译起始因子-3）和组织生长（β-肌动蛋白、结蛋白和角蛋白10）。此外，IUGR增加了参与蛋白水解（蛋白酶体α-5和α-1亚基）、氧化应激反应（清道夫受体蛋白和α-1酸性糖蛋白）和ATP水解（F1-ATP酶）的蛋白质水平。这些新的发现表明，细胞信号缺陷，氧化还原失衡，蛋白质合成减少，蛋白质水解增强可能是负责营养物质的异常吸收和代谢，以及生长减少和发育受损的小肠，肝脏和肌肉在IUGR新生儿的主要机制。
Efficiency of nutrient utilization is high in neonates with normal birth weights but is reduced in those with intrauterine growth restriction (IUGR). However, the underlying mechanisms are largely unknown. This study was conducted with the piglet model and proteomics technology to test the hypothesis that IUGR affects expression of key proteins that regulate growth and development of the small intestine, liver, and muscle, the major organs involved in the digestion, absorption, and metabolism of dietary nutrients. Jejunum, liver, and gastrocnemius muscle were obtained from IUGR and normal birth-weight piglets at birth for analysis of proteomes using the 2-dimensional-PAGE MS technology. The results indicate that IUGR decreased the levels of proteins that regulate immune function (immunoglobulins and annexin A1), oxidative defense (peroxiredoxin 1, transferrin, and zeta-crystallin), intermediary metabolism (creatine kinase, alcohol dehydrogenase, L-lactate dehydrogenase, prostaglandin F synthase, apolipoprotein Al, catecho O-methyltransferase, and phosphoglycerate kinase 1), protein synthesis (eukaryotic translation initiation factor-3), and tissue growth (beta-actin, desmin, and keratin 10) in a tissue-specific manner. In addition, IUGR increased the levels of proteins that are involved in proteolysis (proteasome alpha-5 and alpha-1 subunits), response to oxidative stress (scavenger-receptor protein and alpha-1 acid glycoprotein), and ATP hydrolysis (F1-ATPase). These novel findings suggest that cellular signaling defects, redox imbalance, reduced protein synthesis, and enhanced proteolysis may be the major mechanisms responsible for abnormal absorption and metabolism of nutrients, as well as reduced growth and impaired development of the small intestine, liver, and muscle in IUGR neonates.