title: Proteomic responses of BEAS-2B cells to nontoxic and toxic chromium: Protein indicators of cytotoxicity conversion.
abstract: Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces cytotoxicity and carcinogenesis. To identify those disruptions which are altered in response to cytotoxic Cr (VI) exposures, we measured and compared cytotoxicity and changes in expression and phosphorylation status of 15 critical biochemical pathway regulators in human BEAS-2B cells exposed for 48h to a non-toxic concentration (0.3μM) and a toxic concentration (1.8μM) of Cr (VI) by ELISA techniques. In addition, 43 functional proteins which may be altered in response to pathway signaling changes were identified using two dimensional electrophoresis (2-DE) and mass spectrometry. The proteins and fold changes observed in cells exposed to the non-toxic dose of Cr (VI) (0.3μM) were not necessarily the same as those found in the toxic one (1.8μM). A subset of signaling proteins that were correlated with the cytotoxic responses of human BEAS-2B cells to Cr (VI) treatments were identified. These proteins include regulators of glycolysis, glycogen synthase kinase 3 beta (GSK3β) and phosphoprotein 70 ribosomal protein s6 kinase (p70S6K), a signaling protein associated with oxidative stress and inflammation responses, JNK and metal regulatory transcription factor 1 (MTF-1), and a source of ubiquitin for signaling targeted protein degradation, polyubiquitin C (UBC). In addition, two dimensional gel electrophoresis (2-DE) was applied to identify key alterations in biochemical pathways differentiating between cytotoxic and non-cytotoxic exposures to Cr (VI), including glycolysis and gluconeogenesis, protein degradation, inflammation, and oxidative stress.
authors: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors: Maribel
authors: M
authors: Bruno
authors: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors: Jeffrey
authors: J
authors: Ross
authors: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: ge.yue@epa.gov.
authors: Yue
authors: Y
authors: Ge
mesh_terms: D002274:Carcinogens, Environmental / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002857:Chromium / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D010449:Peptide Mapping; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D000097809:Transcription Factor MTF-1
chemical_list: D002274:Carcinogens, Environmental; D002857:Chromium; D004268:DNA-Binding Proteins; D004785:Environmental Pollutants; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1; C074702:chromium hexavalent ion
keywords: Chromium; Cytotoxicity; ELISA; Metals; Mode of action; Pathways; Protein expression and phosphorylation; Proteomics