Proteomic analysis of the response of human lung cells to uranium.
The industrial use of uranium and particularly of depleted uranium, has pinpointed the need to review its chemical impact on human health. A proteomic approach was used to evaluate the response of a human lung cell line (A549) to uranium. We established the first 2-D reference map of the A549 cell line, identifying 87 spots corresponding to 81 major proteins. Uranium treatment triggered differential expression of 18 spots, of which 14 corresponded to fragments of cytokeratin 8 (CK8) and cytokeratin (CK18) and 1 to peroxiredoxin 1. We probed several hypotheses regarding CK cleavage, and observed that it did not result from caspase or calpain activity. Furthermore, we showed that the fragments are recognised by an anti-ubiquitin antibody (KM691). These results suggest a regulatory pathway involving CK ubiquitinylation or dysfunction in the proteasome-ubiquitin system in response to uranium exposure in human lung cells.
Malard
Véronique
V
Service de Biochimie post-génomique et Toxicologie Nucléaire, DSV/DIEP, CEA VALRHO, Bagnols-sur-Cèze, France. veronique.malard@cea.fr
Prat
Odette
O
Darrouzet
Elisabeth
E
Bérenguer
Frédéric
F
Sage
Nicole
N
Quéméneur
Eric
E
D000595:Amino Acid Sequence; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004798:Enzymes / Q000032:analysis*; D006801:Humans; D007633:Keratins / Q000032:analysis / Q000737:chemistry; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014501:Uranium / Q000494:pharmacology*
D004798:Enzymes; D011506:Proteins; D014501:Uranium; D007633:Keratins