Proteomic identification of carbonylated proteins in the kidney of trichloroethene-exposed MRL+/+ mice

Abstract

Trichloroethene (TCE), a common environmental and occupational pollutant, is associated with multiorgan toxicity. Kidney is one of major target organs affected as a result of TCE exposure. Our previous studies have shown that exposure to TCE causes increased protein oxidation (protein carbonylation) in the kidneys of autoimmune-prone MRL+/+ mice, and suggested a potential role of protein oxidation in TCE-mediated nephrotoxicity. To assess the impact of chronic TCE exposure on protein oxidation, particularly to identify the carbonylated proteins in kidneys, female MRL+/+ mice were treated with TCE at the dose of 2 mg/ml via drinking water for 36 weeks and kidney protein extracts were analyzed for protein carbonyls and carbonylated proteins identified using proteomic approaches (2D gel, Western blot, MALDI TOF/TOF MS/MS, etc.). TCE treatment led to significantly increased protein carbonyls in the kidney protein extracts (20 000 g pellet fraction). Interestingly, among 18 identified carbonylated proteins, 10 were found only in the kidneys of TCE-treated mice, whereas other 8 were present in the kidneys of both control and TCE-treated mice. The identified carbonylated proteins represent skeletal proteins, chaperones, stress proteins, enzymes, plasma protein and proteins involved in signaling pathways. The findings provide a map for further exploring the role of carbonylated proteins in TCE-mediated nephrotoxicity.

• Autoimmune nephritis
• oxidative stress
• protein carbonylation
• proteomics
• trichloroethene