title: A proteomic approach to identification of plutonium-binding proteins in mammalian cells.
abstract: Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry was employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu(4+)-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore™ analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.
authors.affiliation: Chemical Science and Engineering Division, Argonne National Lab, Argonne, IL, USA.
authors.forename: Baikuntha P
authors.initials: BP
authors.lastname: Aryal
authors.forename: Tatjana
authors.initials: T
authors.lastname: Paunesku
authors.forename: Gayle E
authors.initials: GE
authors.lastname: Woloschak
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jensen
mesh_terms: D000818:Animals; D008667:Metalloproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016716:PC12 Cells; D011005:Plutonium / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D040901:Proteomics / Q000379:methods; D051381:Rats
chemical_list: D008667:Metalloproteins; D009419:Nerve Tissue Proteins; D011005:Plutonium