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Quantitative Proteomic Profiles of Androgen Receptor Signaling in the Liver of Fathead Minnows Pimephalus promelas
Citation:
MARTYNIUK, C. J., S. ALVAREZ, S. MCCLUNG, D. L. VILLENEUVE, G. T. ANKLEY, AND N. DENSLOW. Quantitative Proteomic Profiles of Androgen Receptor Signaling in the Liver of Fathead Minnows Pimephalus promelas . Journal of Proteome Research . American Chemical Society, Washington, DC, 8(5):2186-2200, (2009).
Impact/Purpose:
Androgenic chemicals are present in the environment at concentrations that could impair reproductive processes in fish. The objective of this research was to identify proteins altered by an androgen receptor agonist (17â-trenbolone) and antagonist (flutamide) in the liver of female fathead minnows (FHM) exposed to the chemicals singly or as a mixture.. The iTRAQ™ method was used to identify 45 proteins were as differentially altered by one or more treatments (p < 0.05). These proteins were involved in 1) fatty acid metabolism and transport (e.g. enoyl Coenzyme A hydratase 1; fatty acid binding protein10), 2) cellular metabolism (e.g. glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1), 3) general and oxidative stress response (e.g. superoxide dismutase and heat shock proteins), and 4) regulation of transcription and translation (e.g. ribosomal proteins). Cellular pathway analysis suggested additional signaling cascades activated or inhibited for flutamide that may not be androgen receptor mediated. Altered protein abundance correlated with mRNA levels in few cases, indicating that molecular responses were evoked at both transcriptional and translational levels. This study helps demonstrate the potential of using both quantitative genomic and proteomic approaches in toxicology to study the mechanisms of toxicity of endocrine disrupting chemicals.
Description:
Androgenic chemicals are present in the environment at concentrations that impair reproductive processes in fish. The objective of this experiment was to identify proteins altered by an androgen receptor agonist (17â-trenbolone) and antagonist (flutamide) in the liver. Female fathead minnows (FHM) were exposed to a dose of either 17â-trenbolone (0.05, 0.5, or 5 µg/L), flutamide (5, 50, or 500 µg/L), or a mix (500 µg flutamide /L and 0.5 µg 17â-trenbolone/L) for 48 hours. The iTRAQ™ method was used to label peptides after protein digestion from control, 17â-trenbolone-treated (5 µg/L), flutamide-treated (500 µg/L), and a mix of both compounds. Forty-five proteins were differentially altered by one or more treatments (p < 0.05). These proteins were involved in 1) fatty acid metabolism and transport (e.g. enoyl Coenzyme A hydratase 1; fatty acid binding protein10), 2) cellular metabolism (e.g. glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1), 3) general and oxidative stress response (e.g. superoxide dismutase and heat shock proteins), and 4) regulation of transcription and translation (e.g. ribosomal proteins). Cellular pathway analysis suggested additional signaling cascades activated or inhibited for flutamide that may not be androgen receptor mediated. Altered protein abundance correlated with mRNA levels in few cases, indicating that molecular responses were evoked at both transcriptional and translational levels. We demonstrate the potential of using both quantitative genomic and proteomic approaches in toxicology to study the mechanisms of endocrine disrupting chemicals.