Proteomic analysis of hepatic protein profiles in rare minnow (Gobiocypris rarus) exposed to perfluorooctanoic acid.
Proteomic analysis of hepatic protein profiles in rare minnow (Gobiocypris rarus) exposed to perfluorooctanoic acid.
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DOI：
10.1021/pr7008059
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发表时间：
2008-02
影响因子：
4.4
通讯作者：
Yanhong Wei;L. Chan;Dazhi Wang;Hongxia Zhang;Jianshe Wang;Jiayin Dai
中科院分区：
文献类型：
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作者：
Yanhong Wei;L. Chan;Dazhi Wang;Hongxia Zhang;Jianshe Wang;Jiayin Dai
全氟辛酸 (PFOA) 是一种普遍存在的污染物，已被证明会导致肝毒性，并与哺乳动物肝脏肿瘤的发病率有关。先前的许多研究已经根据常规毒理学指标和转录数据描述了 PFOA 的毒性作用。然而，关于蛋白质水平的证据很少。为了进一步了解作用机制并确定 PFOA 暴露的潜在蛋白质生物标志物，二维电泳结合质谱法已被用来鉴定稀有鲫鱼 (Gobiocypris rarus) 在暴露 3、10 和 30 mg/L PFOA 后肝脏中差异表达的蛋白质。比较处理组和对照组的蛋白质谱后，发现雄性和雌性分别有 34 个和 48 个蛋白质点发生丰度改变（> 2 倍）。基质辅助激光解吸/电离 (MALDI) 串联飞行时间质谱 (TOF/TOF) 分析可以明确识别 25 个点，对应 22 种不同的蛋白质。这些蛋白质参与细胞内脂肪酸运输、氧化应激、大分子分解代谢、细胞周期、细胞内Ca2+稳态的维持和线粒体功能。此外，通过男性和女性蛋白质谱的比较，可以清楚地描述对 PFOA 反应的显着性别差异。通过实时 PCR 确定了蛋白质组分析中被 PFOA 改变的九种编码蛋白质的 mRNA 的转录分析。 mRNA 和蛋白质水平之间的一致和差异结果表明，复杂的基因表达调节机制与 PFOA 暴露的反应有关。
Perfluorooctanoic acid (PFOA) is a ubiquitous contaminant that has been shown to lead to hepatoxicity and is implicated in the incidence of liver tumors in mammals. A number of previous studies have described the toxic effects of PFOA based on conventional toxicological indices and transcriptional data. However, little evidence on protein levels is available. To further our understanding of mechanisms of action and identify the potential protein biomarkers for PFOA exposure, two-dimensional electrophoresis coupled with mass spectrometry has been used to identify proteins differentially expressed in the livers of rare minnow ( Gobiocypris rarus) following PFOA exposure of 3, 10, and 30 mg/L. After comparison of the protein profiles from treated and control groups, 34 and 48 protein spots were found altered in abundance (> 2-fold) from males and females, respectively. Matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight mass spectrometry (TOF/TOF) analysis allowed the unambiguous identification of 25 spots, corresponding to 22 different proteins. These proteins were involved in intracellular fatty acid transport, oxidative stress, macromolecule catabolism, the cell cycle, maintenance of intracellular Ca2+ homeostasis, and mitochondrial function. In addition, marked gender differences in response to PFOA have been well-described from the comparison of the male and female protein profiles. Transcriptional analysis of nine mRNAs encoding proteins altered by PFOA in the proteome analysis was determined by real-time PCR. The consistent and discrepant results between mRNA and protein levels suggested that complicated regulatory mechanisms of gene expression were implicated in the response to PFOA exposure.