Multifactorial comparative proteomic study of cytochrome P450 2E1 function in chronic alcohol administration.
Multifactorial comparative proteomic study of cytochrome P450 2E1 function in chronic alcohol administration.
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DOI：
10.1371/journal.pone.0092504
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Wang Y;Kou Y;Wang X;Cederbaum A;Wang R
使用iTRAQ技术，可以进行多因子比较蛋白质组学研究。在本研究中，为了全面了解乙醇、CYP2E1和性别对肝损伤的影响，并进一步了解其潜在的分子机制，我们使用iTRAQ定量分析了不同性别小鼠、野生型小鼠与CYP2E1敲除小鼠、正常饮食与酒精饮食小鼠8种情况下的小鼠肝脏蛋白质组。一系列的统计和生物信息学分析探索简化和澄清多因子比较蛋白质组学数据。首先，通过主成分分析，在慢性酒精中毒模型的所有实验条件下，CYP2E1、FAM25、CA3、BHMT、HIBADH和ECHS1这六种参与氧化还原、能量和脂质代谢以及氨基酸代谢的蛋白质被确定为表达差异最大的基因产物。其次，分层聚类分析显示，与乙醇和性别因素相比，CYP2E1基因敲除在总体差异蛋白表达中起主要作用。此外，两两多重比较显示，在乙醇处理的野生型和CYP2E1敲除小鼠中，只有显著的表达差异。第三，k均值聚类分析表明，CYP2E1敲除对乙醇诱导的氧化应激和脂质氧化具有逆转作用。更重要的是，蛋白质组学数据的IPA分析推断，慢性酒精喂养和CYP2E1敲除调控的两个上游调控因子NRF2和PPARα的基因表达参与了乙醇诱导的氧化应激和脂质氧化。本研究提供了一个有效的综合数据分析策略，以比较多种生物因素，有助于酒精对肝脏的生化影响。质谱蛋白质组学数据已存入ProteomeXchange，数据集标识符为PXD000635。
With the use of iTRAQ technique, a multifactorial comparative proteomic study can be performed. In this study, to obtain an overview of ethanol, CYP2E1 and gender effects on liver injury and gain more insight into the underlying molecular mechanism, mouse liver proteomes were quantitatively analyzed using iTRAQ under eight conditions including mice of different genders, wild type versus CYP2E1 knockout, and normal versus alcohol diet. A series of statistical and bioinformatic analyses were explored to simplify and clarify multifactorial comparative proteomic data. First, with the Principle Component analysis, six proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation reduction, energy and lipid metabolism and amino acid metabolism, were identified as the most differentially expressed gene products across all of the experimental conditions of our chronic alcoholism model. Second, hierarchical clustering analysis showed CYP2E1 knockout played a primary role in the overall differential protein expression compared with ethanol and gender factors. Furthermore, pair-wise multiple comparisons have revealed that the only significant expression difference lied in wild-type and CYP2E1 knockout mice both treated with ethanol. Third, K-mean clustering analysis indicated that the CYP2E1 knockout had the reverse effect on ethanol induced oxidative stress and lipid oxidation. More importantly, IPA analysis of proteomic data inferred that the gene expressions of two upstream regulators, NRF2 and PPARα, regulated by chronic alcohol feeding and CYP2E1 knockout, are involved in ethanol induced oxidative stress and lipid oxidation. The present study provides an effectively comprehensive data analysis strategy to compare multiple biological factors, contributing to biochemical effects of alcohol on the liver. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with data set identifier of PXD000635.
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影响因子：
8.2
作者：
BRUDZYNSKI, K;MARTINEZ, V;GUPTA, RS
通讯作者：
GUPTA, RS
影响因子：
2
作者：
Jia X;Yin L;Feng Y;Peng X;Ma F;Yao Y;Liu X;Zhang Z;Yuan Z;Zhang L
通讯作者：
Zhang L
影响因子：
4.4
作者：
Habich, C;Baumgart, K;Burkart, V
通讯作者：
Burkart, V
影响因子：
7.3
作者：
Banerjee, A;Apte, UM;Ramaiah, SK
通讯作者：
Ramaiah, SK
影响因子：
4.6
作者：
Fogle, Rachel L.;Hollenbeak, Christopher S.;Lynch, Christopher J.
通讯作者：
Lynch, Christopher J.