Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity.
The industrial use of uranium, in particular depleted uranium, has pin-pointed the need to review its chemical impact on human health. Global methodologies, applied to the field of toxicology, have demonstrated their applicability to investigation of fine molecular mechanisms. This report illustrate the power of toxicogenomics to evaluate the involvement of certain genes or proteins in response to uranium. We particularly show that 25% of modulated genes concern signal transduction and trafficking, that the calcium pathway is heavily disturbed and that nephroblastomas-related genes are involved (WIT-1, STMN1, and STMN2). A set of 18 genes was deregulated whatever the concentration of toxicant, which could constitute a signature of uranium exposure. Moreover, a group of downregulated genes, with corresponding disappearing proteins (HSP90, 14-3-3 protein, HMGB1) in two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), are good candidates for use as biomarkers of uranium effects. These results reveal a cross-checking between transcriptomic and proteomic technologies. Moreover, our temporal gene expression profiles suggest the existence of a concentration threshold between adaptive response and severe cell deregulation. Our results confirm the involvement of genes already described and also provide new highlights on cellular response to uranium.
Prat
Odette
O
Service de Biochimie post-génomique et Toxicologie Nucléaire, F-30207 Bagnols-sur-Cèze, France. odette.prat@cea.fr
Berenguer
Frédéric
F
Malard
Véronique
V
Tavan
Emmanuelle
E
Sage
Nicole
N
Steinmetz
Gérard
G
Quemeneur
Eric
E
D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport / Q000187:drug effects; D020543:Proteome / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014501:Uranium / Q000633:toxicity*
D015415:Biomarkers; D020543:Proteome; D012333:RNA, Messenger; D014501:Uranium