Quantitative analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced proteome alterations in 5L rat hepatoma cells using isotope-coded protein labels.
In an effort to contribute to a better understanding of the hepatic toxicity of the ubiquitous environmental pollutant and hepatocarcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a comprehensive quantitative proteome analysis was performed on 5L rat hepatoma cells exposed to 1 nM TCDD for 8 h. Changes in the abundances of individual protein species in TCDD-treated cells as compared to untreated cells were analysed using the nongel-based isotope-coded protein label (ICPL) method [Schmidt, A., Kellermann, J., Lottspeich, F., Proteomics 2005, 5, 4-15]. 89 proteins were identified as up- or down-regulated by TCDD. For the majority of the altered proteins, an impact of TCDD on their abundance had not been known before. Due to the physicochemical properties or the translational regulation of a large number of the affected proteins, their alteration would have escaped detection by gel-based methods for proteome analysis and by standard mRNA expression profiling, respectively. The identified proteins with TCDD-altered abundance include several proteins implicated in cell cycle regulation, growth factor signalling and the control of apoptosis. The results thus provide new starting-points for the investigation of specific aspects of the toxicity and carcinogenicity of dioxin in liver.
GSF - Forschungszentrum für Umwelt und Gesundheit, Institut für Toxikologie, Neuherberg, Germany.
Hakan
H
Sarioglu
Stefanie
S
Brandner
Carola
C
Jacobsen
Thomas
T
Meindl
Alexander
A
Schmidt
Josef
J
Kellermann
Friedrich
F
Lottspeich
Ulrich
U
Andrae
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000494:pharmacology; D015536:Down-Regulation; D004785:Environmental Pollutants; D008113:Liver Neoplasms / Q000378:metabolism*; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry; D000072317:Polychlorinated Dibenzodioxins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
D004785:Environmental Pollutants; D010455:Peptides; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1