title: Toxic metal proteomics: reaction of the mammalian zinc proteome with Cd²⁺.
abstract: The hypothesis was tested that Cd(2+) undergoes measureable reaction with the Zn-proteome through metal ion exchange chemistry. The Zn-proteome of pig kidney LLC-PK1 cells is relatively inert to reaction with competing ligands, including Zinquin acid, EDTA, and apo-metallothionein. Upon reaction of Cd(2+) with the Zn-proteome, Cd(2+) associates with the proteome and near stoichiometric amounts of Zn(2+) become reactive with these chelating agents. The results strongly support the hypothesis that Cd(2+) displaces Zn(2+) from native proteomic binding sites resulting in the formation of a Cd-proteome. Mobilized Zn(2+) becomes adventitiously bound to proteome and available for reaction with added metal binding ligands. Cd-proteome and Zn-metallothionein readily exchange metal ions, raising the possibility that this reaction restores functionality to Cd-proteins. In a parallel experiment, cells were exposed to Cd(2+) and pyrithione briefly to generate substantial proteome-bound Cd(2+). Upon transition to a Cd(2+) free medium, the cells generated new metallothionein protein over time that bound most of the proteomic Cd(2+) as well as additional Zn(2+).
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
authors: Mohammad Ali
authors: MA
authors: Namdarghanbari
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
authors: Joseph
authors: J
authors: Bertling
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
authors: Susan
authors: S
authors: Krezoski
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA. Electronic address: petering@uwm.edu.
authors: David H
authors: DH
authors: Petering
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002614:Chelating Agents / Q000737:chemistry; D004492:Edetic Acid / Q000737:chemistry; D018374:LLC-PK1 Cells; D008668:Metallothionein / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D013552:Swine; D015032:Zinc / Q000378:metabolism
chemical_list: D001059:Apoproteins; D002614:Chelating Agents; D020543:Proteome; D002104:Cadmium; D008668:Metallothionein; D004492:Edetic Acid; D015032:Zinc
keywords: Cadmium; Metal exchange; Metallothionein; Zinc proteome