The c-Abl signaling network in the radioadaptive response

Chi-Min, Yuan

doi:10.2172/1116567

Title: The c-Abl signaling network in the radioadaptive response

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Abstract

The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting in a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the thresholdmore »« less

Authors:

Chi-Min, Yuan ^[1]

Univ. of Texas, San Antonio, TX (United States)

Publication Date:: Tue Jan 28 00:00:00 EST 2014

Research Org.:: The University of Texas Health Science Center, San Antonio, TX (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1116567

Report Number(s):: Final Report

DOE Contract Number:: SC0002560

Resource Type:: Technical Report

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES

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                    Chi-Min, Yuan. The c-Abl signaling network in the radioadaptive response.  United States: N. p., 2014. 
        Web.  doi:10.2172/1116567.

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                    Chi-Min, Yuan. The c-Abl signaling network in the radioadaptive response.  United States.  https://doi.org/10.2172/1116567

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                    Chi-Min, Yuan. 2014.  
        "The c-Abl signaling network in the radioadaptive response".  United States.  https://doi.org/10.2172/1116567.  https://www.osti.gov/servlets/purl/1116567.

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@article{osti_1116567,

  title        = {The c-Abl signaling network in the radioadaptive response},

  author       = {Chi-Min, Yuan},

  abstractNote = {The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting in a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.},

  doi          = {10.2172/1116567},

  url          = {https://www.osti.gov/biblio/1116567},
  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {Tue Jan 28 00:00:00 EST 2014},

  month        = {Tue Jan 28 00:00:00 EST 2014}

}

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