Molecular and biochemical biomarkers in environmental monitoring: a comparison of biotransformation and antioxidant defense systems in multiple tissues. (Special Issue: Jubileum.)

摘要

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 gamma -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.