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运用差异蛋白质组学分析研究三氯乙烯对 L-02 肝细胞的适应性反应。

An investigation of hormesis of trichloroethylene in L-02 liver cells by differential proteomic analysis.

机构信息

Toxicology Laboratory, Shenzhen Center for Disease Control and Prevention, 518020 Shenzhen, Guangdong, People's Republic of China.

出版信息

Mol Biol Rep. 2009 Nov;36(8):2119-29. doi: 10.1007/s11033-008-9424-z. Epub 2008 Dec 25.

DOI:10.1007/s11033-008-9424-z
PMID:19109764
Abstract

Hormesis is the dose-response pattern of the biological responses to toxic chemicals, characterized by low-dose stimulation and high-dose inhibition. Although it is known that some cell types exhibit an adaptive response to low levels of cytotoxic agents, its molecular mechanism is still unclear and it has yet to be established whether this is a universal phenomenon that occurs in all cell types in response to exposure to every chemical. Trichloroethylene (TCE) is an organic solvent widely used and is released into the atmosphere from industrial degreasing operations. Acute (short-term) and chronic (long-term) inhalation exposure to trichloroethylene can affect the human health. In order to elucidate a cell-survival adaptive response of L-02 liver cells exposed to low dose of TCE, CCK-8 assay was used to assess cytotoxicity, and examined the possible mechanisms of hormesis by proteomics technology. We found that exposure of L-02 liver cells to low level of TCE resulted in adaptation to further exposure to higher level, about 1,000 protein-spots were obtained by two-dimensional electrophoresis (2-DE) and five protein spots were identified by matrix-assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry sequencing of tryptic peptides. Our results suggest that a relationship may exist between identified proteins and TCE-induced hormesis, which are very useful for further study of the mechanism and risk assessment of TCE.

摘要

中文译文:

毒物兴奋效应是指生物对有毒化学物质的反应的剂量-反应模式,其特征是低剂量刺激和高剂量抑制。虽然已知某些细胞类型对细胞毒性剂的低水平表现出适应性反应,但它的分子机制尚不清楚,也尚未确定这是否是所有细胞类型在暴露于每种化学物质时都会发生的普遍现象。三氯乙烯(TCE)是一种广泛使用的有机溶剂,从工业脱脂作业中释放到大气中。急性(短期)和慢性(长期)吸入三氯乙烯会影响人类健康。为了阐明暴露于低剂量 TCE 的 L-02 肝细胞的细胞存活适应性反应,我们使用 CCK-8 测定法评估细胞毒性,并通过蛋白质组学技术研究毒物兴奋效应的可能机制。我们发现,L-02 肝细胞暴露于低水平的 TCE 会导致对更高水平暴露的适应性,通过二维电泳(2-DE)获得了约 1000 个蛋白斑点,通过基质辅助激光解吸/电离质谱和胰蛋白酶肽串联质谱测序鉴定了 5 个蛋白斑点。我们的结果表明,鉴定出的蛋白质与 TCE 诱导的毒物兴奋效应之间可能存在关系,这对于进一步研究 TCE 的机制和风险评估非常有用。

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Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology.毒理学的觉醒:毒物兴奋效应作为毒理学核心支柱的重生。
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Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity.
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