Prenatal alcohol exposure alters phosphorylation and glycosylation of proteins in rat offspring liver
Prenatal alcohol exposure alters phosphorylation and glycosylation of proteins in rat offspring liver
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DOI：
10.1002/pmic.200800969
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发表时间：
2010-02-01
期刊：
影响因子：
3.4
通讯作者：
Nyomba, B. L. Gregoire
中科院分区：
文献类型：
--
作者：
Fofana, Bourlaye;Yao, Xing-Hai;Nyomba, B. L. Gregoire
为了更深入地了解子宫内暴露于酒精的大鼠后代中发生的翻译和PTM，进行了2-D PAGE、总、磷酸化和糖蛋白染色以及MALDI-MS/MS和数据库搜索。结果，根据倍数变化的表达，揭示了产前酒精暴露在7天和3个月大的大鼠的总蛋白表达下调。有一个上调的蛋白磷酸化，但下调糖基化产前酒精暴露在两个年龄组。为31.每组检测蛋白质斑点，差异表达的蛋白质被鉴定为铁蛋白轻链、醛酮还原酶、肿瘤排斥抗原GP 96、果糖-1，6-二磷酸酶、甘油-3-磷酸脱氢酶、苹果酸脱氢酶和γ-肌动蛋白。在蛋白质如钙调蛋白、谷胱甘肽S-转移酶、葡萄糖调节蛋白58、α-烯醇化酶、真核翻译延伸因子1 β-2、核糖蛋白大P2、胍丁胺酶、鸟氨酸氨基甲酰基转移酶、喹啉磷酸核糖基转移酶、甲亚胺基转移酶环脱氨酶和肌动蛋白中观察到磷酸化增加。此外，腺苷激酶、腺苷高半胱氨酸水解酶和3-羟基邻氨基苯甲酸双加氧酶的糖基化减少。受这些蛋白质改变影响的途径包括细胞信号传导、细胞应激、蛋白质合成、细胞骨架以及葡萄糖、氨基酸、腺苷和能量代谢。产前酒精可提高产酸酶果糖-1，6-二磷酸酶的活性。这些观察结果可能具有重要的生理意义。
To gain more insights into the translational and PTM that occur in rat offspring exposed to alcohol in utero, 2-D PAGE with total, phospho- and glycoprotein staining and MALDI-MS/MS and database searching were conducted. The results, based on fold-change expression, revealed a down-regulation of total protein expression by prenatal alcohol exposure in 7-day-old and 3-month-old rats. There was an up-regulation of protein phosphorylation but a down-regulation of glycosylation by prenatal alcohol exposure in both age groups. Of 31. protein spots examined per group, differentially expressed proteins were identified as ferritin light chain, aldo-keto reductase, tumor rejection antigen gp96, fructose-1, 6-bisphosphatase, glycerol-3-phosphate dehydrogenase, malate dehydrogenase, and gamma-actin. Increased phosphorylation was observed in proteins such as calmodulin, gluthatione S-transferase, glucose regulated protein 58, alpha-enolase, eukaryotic translation elongation factor 1 beta-2, riboprotein large P2, agmatinase, ornithine carbamoyltransferase, quinolinate phosphoribosyltransferase, formimidoyltransferase cyclodeaminase, and actin. In addition, glycosylation of adenosine kinase, adenosylhomocysteine hydrolase, and 3-hydroxyanthranilate dioxygenase was reduced. Pathways affected by these protein alterations include cell signaling, cellular stress, protein synthesis, cytoskeleton, as well as glucose, aminoacid, adenosine and energy metabolism. The activity of the gluconeogenic enzyme fructose-1, 6-bisphosphatase was elevated by prenatal alcohol. The observations may have important physiological implications.