A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Baikuntha P. Aryal; Tatjana Paunesku; Gayle E. Woloschak; Chuan He; Mark P. Jensen

doi:10.1016/j.jprot.2011.11.023

A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Baikuntha P. Aryal, Tatjana Paunesku, Gayle E. Woloschak, Chuan He, Mark P. Jensen^*

^*Corresponding author for this work

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1505-1514
Number of pages	10
Journal	Journal of Proteomics
Volume	75
Issue number	5
DOIs	https://doi.org/10.1016/j.jprot.2011.11.023
State	Published - Feb 16 2012

Funding

We gratefully thank the Donald Danforth Plant Science Center, Proteomics & Mass Spectrometry Facility, St. Louis, MO for the LC–MS/MS analysis. This work was supported by the University of Chicago and the Department of Energy under section H.35 of U.S. Department of Energy contract no. DE-AC02-06CH11357 awarded to UChicago Argonne, LLC, operator of Argonne National Laboratory and by the U.S. Department of Energy, Office of Basic Energy Sciences under contract no. DE-AC02-06CH11357 . The supporting organizations had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or the decision to submit the article for publication.

Keywords

2-D gel electrophoresis
GO process
IMAC
LC-MS/MS
PC12 cells
Plutonium-binding proteins

ASJC Scopus subject areas

Biophysics
Biochemistry

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10.1016/j.jprot.2011.11.023

Cite this

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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{\texttrademark} analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.",

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note = "Funding Information: We gratefully thank the Donald Danforth Plant Science Center, Proteomics & Mass Spectrometry Facility, St. Louis, MO for the LC–MS/MS analysis. This work was supported by the University of Chicago and the Department of Energy under section H.35 of U.S. Department of Energy contract no. DE-AC02-06CH11357 awarded to UChicago Argonne, LLC, operator of Argonne National Laboratory and by the U.S. Department of Energy, Office of Basic Energy Sciences under contract no. DE-AC02-06CH11357 . The supporting organizations had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or the decision to submit the article for publication. ",

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AU - Jensen, Mark P.

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N2 - 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.

AB - 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.

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A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Abstract

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Keywords

ASJC Scopus subject areas

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