Pulmonary Proteome and Protein Networks in Response to the Herbicide Paraquat in Rats.
Pulmonary Proteome and Protein Networks in Response to the Herbicide Paraquat in Rats.
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DOI：
10.4172/jpb.1000354
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Li QX
中科院分区：
文献类型：
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作者：
Cho IK;Jeong M;You AS;Park KH;Li QX
百草枯（Paraquat，PQ）是目前世界上使用最广泛的除草剂之一。PQ在摄入时对人体有毒，并可能导致急性呼吸窘迫综合征。为了研究PQ对肺组织的分子干扰作用，以25 mg/kg体重的剂量给Sprague道利雄性大鼠喂食PQ，共20次，共4周。通过对肺组织蛋白质组的分析，研究PQ对细胞过程和生物学途径的影响。在检测到的蛋白质中，与无PQ对照相比，PQ暴露大鼠肺组织中分别有321和254种蛋白质过度表达和表达不足。对所有过度表达和表达不足的蛋白质进行了Inflamity Pathway分析，以创建25个生物网络和38个相互作用的蛋白质簇的通路。过度表达的蛋白质涉及C-jun-amino-terminal kinase途径、caveolae介导的内吞信号、心血管-癌症-呼吸途径、网格蛋白介导的内吞调节、非小细胞肺癌信号、肺动脉高压、谷氨酸受体、免疫应答和血管生成。在PQ处理的肺中，在p53信号通路、丝裂原活化蛋白激酶信号通路、软骨发育和血管生成抑制中出现代表性不足的蛋白。结果提示，PQ可能通过产生活性氧，损伤MAPK/p53信号通路，促进肺血管新生，抑制肺细胞凋亡。
Paraquat (PQ) has been one of the most widely used herbicides in the world. PQ, when ingested, is toxic to humans and may cause acute respiratory distress syndrome. To investigate molecular perturbation in lung tissues caused by PQ, Sprague Dawley male rats were fed with PQ at a dose of 25 mg/kg body weight for 20 times in four weeks. The effects of PQ on cellular processes and biological pathways were investigated by analyzing proteome in the lung tissues in comparison with the control. Among the detected proteins, 321 and 254 proteins were over-represented and under-represented, respectively, in the PQ-exposed rat lung tissues in comparison with the no PQ control. All over- and under-represented proteins were subjected to Ingenuity Pathway Analysis to create 25 biological networks and 38 pathways of interacting protein clusters. Over-represented proteins were involved in the C-jun-amino-terminal kinase pathway, caveolae-mediated endocytosis signaling, cardiovascular-cancer-respiratory pathway, regulation of clathrin-mediated endocytosis, non-small cell lung cancer signaling, pulmonary hypertension, glutamate receptor, immune response and angiogenesis. Under-represented proteins occurred in the p53 signaling pathway, mitogen-activated protein kinase signaling pathway, cartilage development and angiogenesis inhibition in the PQ-treated lungs. The results suggest that PQ may generate reactive oxygen species, impair the MAPK/p53 signaling pathway, activate angiogenesis and depress apoptosis in the lungs.