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首页> 外文期刊>Journal of proteome research >DIGE-Based Protein Expression Analysis of B[a]P-Exposed Hepatoma Cells Reveals a Complex Stress Response Including Alterations in Oxidative Stress, Cell Cycle Control, and Cytoskeleton Motility at Toxic and Subacute Concentrations
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DIGE-Based Protein Expression Analysis of B[a]P-Exposed Hepatoma Cells Reveals a Complex Stress Response Including Alterations in Oxidative Stress, Cell Cycle Control, and Cytoskeleton Motility at Toxic and Subacute Concentrations

机译：B [a] P暴露的肝癌细胞的基于DIGE的蛋白质表达分析揭示了复杂的应激反应，包括在有毒和亚急性浓度下的氧化应激改变，细胞周期控制和细胞骨架运动。

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Although the effects of high concentrations of the carcinogen benzo[a]pyrene (B[a]P) have been studied extensively, little is known about its effects at subacute toxic concentrations, which are typical for environmental pollutants. We exposed murine Hepa1c1c7 cells to a toxic concentration (5 μM) and a subacute concentration (50 nM) of B[a]P over a period of 2?24 h to differentiate between acute and pseudochronic effects and conducted a time-course analysis of B[a]P-influenced protein expression by DIGE. In total, a set of 120 spots were found to be significantly altered due to B[a]P exposure of which 112 were subsequently identified by mass spectrometry. Clustering and principal component analysis were conducted to identify sets of proteins responding in a concerted manner to the exposure. Our results indicate an immediate response to the contaminant at the protein level and demonstrate that B[a]P exposure alters the cellular response by disturbing proteins involved in oxidative stress, cell cycle regulation, apoptosis, and cytoskeleton organization. Furthermore, network analysis of protein?protein interactions revealed a complex network of interacting, B[a]P-regulated proteins mostly belonging to the cytoskeleton organization and several signal transduction pathways.
机译：尽管已经对高浓度致癌物苯并[a] py（B [a] P）的影响进行了广泛研究，但对于亚急性毒性浓度（对于环境污染物而言通常如此）的影响却鲜为人知。我们将小鼠Hepa1c1c7细胞在2？24小时内暴露于B [a] P的毒性浓度（5μM）和亚急性浓度（50 nM）的B [a] P中，以区分急性和拟慢性效应，并对时相分析DIGE对B [a] P影响的蛋白表达。总计，发现一组120个斑点由于B [a] P暴露而发生了显着变化，其中112个斑点随后通过质谱鉴定。进行了聚类和主成分分析，以鉴定以一致的方式响应暴露的蛋白质组。我们的结果表明在蛋白质水平上对污染物的即时反应，并表明B [a] P暴露通过干扰涉及氧化应激，细胞周期调节，细胞凋亡和细胞骨架组织的蛋白质来改变细胞反应。此外，对蛋白质与蛋白质相互作用的网络分析揭示了相互作用的，受B [a] P调节的蛋白质的复杂网络，这些蛋白质主要属于细胞骨架组织和几种信号转导途径。

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