Proteomic characterization of rat liver exposed to 2,3,7,8-tetrachlorobenzo-p-dioxin.

Dioxins are a class of polyhalogenated aromatic hydrocarbons that induce a wide spectrum of toxic responses in experimental animals. In this study, 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD) was exposed to two SD rat groups; one group for short-term exposure at a single dose of 1, 10, 20 and 50 mug/kg body weight (group 1) and the other for long-term exposure at daily and-low dose of 0.01, 0.1, 1 and 2.5 microg/kg body weight (group 2) for a month. Two-dimensional electrophoresis (2-DE) was utilized to resolve the protein profile of rat liver exposed to TCDD at different doses. In the analysis of 2-DE of the group 1, two new-expressed spots and seven volume-increased spots were detected and identified by ESI-Q-TOF MS/MS; especially, proteasome subunit beta type 3 was increased in all doses. In addition, in the group 2, six volume-increased spots were screened; particularly, histidine triad nucleotide binding protein was increased in both 0.1 microg/kg dose and 1 microg/kg dose. The identified proteins were confirmed using Western blot. Among the identified proteins, apolipoprotein A-IV may protect lipid peroxidation and atherosclerosis induced by TCDD exposure and the expression level of phosphoglycerate mutase increases due to hyperthyroidism induced by TCDD exposure.

Analysis of proteins expressed in rat plasma exposed to dioxin using 2-dimensional gel electrophoresis.

Dioxins are a class of polyhalogenated aromatic hydrocarbons that induces a wide spectrum of toxic responses in animals. In this study, two groups of Sprague-Dawley rats were exposed to 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD); one group received short-term exposure at a single dose of 1, 10, 20 or 50 microg/kg body weight and the other received long-term exposure to a daily low dose of 0.01, 0.1, 1 or 2.5 microg/kg body weight for one month. Two-dimensional electrophoresis was utilized to resolve the protein profile of rat plasma exposed to TCDD at different doses. One novel and three volume-increased spots were identified and characterized by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and electrospray-ionization on quadropole-TOF2 mass spectrometry. The novel protein was identified as plasma glutathione peroxidase precursor and the volume-increased proteins were cytokeratin 8 polypeptide, Ig lambda-1 chain C region and Ig lambda-2 chain C region. These proteins may be used as biomarkers to diagnose dioxin exposure and may help in understanding the toxic effects of dioxins.

Monitoring protein expression by proteomics: human plasma exposed to benzene.

Low levels and long term exposure to benzene is associated with hematotoxicity including aplastic anemia, acute myelogenous leukemia, and lymphoma. Current biomonitoring methods such as urinary phenol, S-phenylmercapturic acid, and trans-trans muconic acid were found to be unreliable as analytical methods to detect benzene exposure. Therefore, to search for a specific protein for biomonitoring benzene exposure, we investigated plasma proteins from workers (n = 50) at a printing company who were exposed to benzene, by two-dimensional gel electrophoresis. The protein profiles are significantly different (p < 0.05) between benzene exposed and unexposed groups, as identified by matrix-assisted laser desorption ionization/time of flight mass spectrometry and confirmed by Western blot analyses. T cell receptor beta chain (TCR beta), FK506-binding protein, and matrix metalloproteinase-13 were expressed only in benzene exposed workers. In addition, interleukin-4 receptor alpha chain and T cell surface glycoprotein CD1b precursor were found to be up-regulated in the plasma of benzene exposed workers. When we treated Jurkat cells with benzene (10 microM-10 mM), TCR beta expression was increased in the membrane more than 6-9-fold compared to untreated cells. In addition, the amount of TCR beta released into the culture media, at benzene concentrations greater than 50 microM, increased up to 10 mM. Therefore, TCR beta levels in plasma could be used as a biomarker and a possible therapeutic target for benzene exposure.