Protein carbonyl formation in response to propiconazole-induced oxidative stress.
Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propiconazole-induced toxicity. To understand the contribution of oxidative stress on toxicity at the protein level, we developed an integrated approach for the systematic measurement of protein oxidation in the livers from propiconazole-treated mice. Liver protein carbonylation increased significantly after treatment with propiconazole, demonstrating propiconazole-associated induction of oxidative stress. Utilizing two-dimensional gel electrophoresis (2-DE), immunoblotting, and mass spectrometry, we identified 17 carbonylated proteins that were altered with varying intensities by propiconazole treatment. The potential effects of protein carbonylation on protein functions and cellular activities in the liver of propiconazole-treated mice were further investigated. A significant negative correlation between protein carbonylation and cytochrome c reductase activity was found. We conclude that glycolysis, mitochondrial respiratory chain, ATP production, amino acid metabolism, CO2 hydration, cellular antioxidant defense and detoxification system, and tetrahydrobiopterin pathways are affected by oxygen radicals in the livers of propiconazole-treated mice. This study suggests a mode of propiconazole-induced toxicity in mouse liver which primarily involves oxidative damage to cellular proteins.
Bruno
Maribel
M
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Moore
Tanya
T
Nesnow
Stephen
S
Ge
Yue
Y
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D005659:Fungicides, Industrial / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014230:Triazoles / Q000494:pharmacology* / Q000633:toxicity
D005659:Fungicides, Industrial; D014230:Triazoles; C045950:propiconazole