Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

Chen, Xian

Title: Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

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Abstract

The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information,more »« less

Authors:: Chen, Xian

Publication Date:: Wed Oct 23 00:00:00 EDT 2013

Research Org.:: University of North Carolina-Chapel Hill

Sponsoring Org.:: USDOE Office of Science (SC)

OSTI Identifier:: 1097124

Report Number(s):: ER64422

DOE Contract Number:: FG02-07ER64422

Resource Type:: Technical Report

Country of Publication:: United States

Language:: English

Subject:: 74 ATOMIC AND MOLECULAR PHYSICS; 59 BASIC BIOLOGICAL SCIENCES; Low-dose radiation, molecular pathways, proteomics, signaling, acute or chronic radiation

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                    Chen, Xian. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects.  United States: N. p., 2013. 
        Web.

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                    Chen, Xian. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects.  United States.

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                    Chen, Xian. 2013.  
        "Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects".  United States.

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@article{osti_1097124,

  title        = {Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects},

  author       = {Chen, Xian},

  abstractNote = {The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information, we will perform a computational network analysis to elucidate a global pathway/mechanisms underlying cellular responses to real-time low-dose IR. Similarly, we will extend our scheme to investigate systematically those induction/transmission pathways occurring in a fibroblast-epithelial interacting model in which the bystander cell (fibroblast) monitor the IR damage to the target cell (epithelial cell). The results will provide the proteome base (molecular mechanisms/pathways for signaling) for the low dose radiation-induced essential tissue environment interactions, including cell-cell, extracellular matrix and extracellular paracrine interactions.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/1097124},
  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {Wed Oct 23 00:00:00 EDT 2013},

  month        = {Wed Oct 23 00:00:00 EDT 2013}

}

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