Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.
Aquat Toxicol. 2011 Oct;105(3-4 Suppl):56-66. doi: 10.1016/j.aquatox.2011.06.014. Epub 2011 Jun 23.
The cytochrome P450 pathway and antioxidant responses are known for their responsiveness to environmental pollutants and are frequently used as biomarkers at the transcriptional, translational and catalytic levels. Although molecular responses are often assumed to reflect similar changes in enzyme function, several factors can influence intracellular effects, including mRNA stability and protein turnover, signal sensing and transduction, post-translational modifications of proteins, and multiple mode of action of chemicals in complex mixtures. The aim of this study was to use experimental data for a general discussion on the importance of mechanisms modulating transcriptional and catalytic responses of these pathways, and the resulting implications for environmental monitoring. The European eel Anguilla anguilla was selected as fish model to compare the effects of polluted sediments on gene expression and functional levels of cytochrome P450, glutathione S-transferases, UDP-glucoronosyl transferases, catalase, glutathione peroxidases, superoxide dismutase, glutathione, glutathione reductase, glucose 6-phosphate dehydrogenase and γ-glutamylcysteine ligase in the liver and gills. The overall results confirmed significant changes in gene transcription related to biotransformation and oxyradical metabolism, but also supported the evidence of a frequent dissociation between mRNA expression and protein activity. More similar trends of variations and exposure-dependent relationships was observed in the liver for transcriptional and catalytic responses of those pathways closely regulated by specific interactions between substrate, transcription factors, gene and metabolizing protein (i.e. phase I and phase II). On the other hand, the lower metabolism and the cellular machinery of gill cells may prevent elevated transcriptional responsiveness to be translated to an adequate functional response of a protein. Relationships between transcriptional and catalytic effects were often inconsistent for antioxidant responses confirming the complexity of interactions between exposure to chemical pollutants and regulation of oxidative stress responses. Oxidative stress responses may not necessarily be associated with transcriptional variations of genes, but rather with post-translational modifications of proteins. These mechanisms are just beginning to be revealed in marine organisms, but their characterization will be fundamental for better understanding of the implications of variations in gene expressions according to system, tissue, intensity and duration of exposure.
细胞色素 P450 途径和抗氧化反应以其对环境污染物的反应性而闻名,经常在转录、翻译和催化水平上用作生物标志物。尽管分子反应通常被认为反映了酶功能的相似变化,但有几个因素会影响细胞内的影响,包括 mRNA 的稳定性和蛋白质周转率、信号感应和转导、蛋白质的翻译后修饰以及复杂混合物中化学物质的多种作用模式。本研究的目的是利用实验数据对调节这些途径转录和催化反应的机制的重要性进行一般性讨论,并对环境监测产生影响。选择欧洲鳗鱼 Anguilla anguilla 作为鱼类模型,比较受污染沉积物对肝脏和鳃中细胞色素 P450、谷胱甘肽 S-转移酶、UDP-葡糖醛酸转移酶、过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶、谷胱甘肽、谷胱甘肽还原酶、葡萄糖 6-磷酸脱氢酶和 γ-谷氨酰半胱氨酸连接酶的基因表达和功能水平的影响。总体结果证实了与生物转化和氧化应激代谢相关的基因转录发生了显著变化,但也支持了 mRNA 表达与蛋白质活性经常分离的证据。在肝脏中,那些受特定底物、转录因子、基因和代谢蛋白之间相互作用密切调节的途径的转录和催化反应表现出更相似的变化趋势和暴露依赖性关系(即 I 相和 II 相)。另一方面,鳃细胞的代谢和细胞机制可能会阻止转录响应的升高转化为蛋白质的适当功能响应。抗氧化反应的转录和催化效应之间的关系通常不一致,这证实了化学污染物暴露与氧化应激反应调节之间相互作用的复杂性。氧化应激反应不一定与基因转录变化相关,而是与蛋白质的翻译后修饰相关。这些机制在海洋生物中才刚刚开始被揭示,但它们的特征对于根据系统、组织、暴露强度和持续时间更好地理解基因表达变化的意义至关重要。