title: Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response.
abstract: Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure.
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lall
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ganapathy
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Xiao
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Su
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shadfan
authors.affiliation: 1] Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Asara
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Ha
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Ben-Sahra
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Manning
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Little
authors.affiliation: Department of Genetics and Complex Diseases, Harvard University School of Public Health, Boston, MA, USA.
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001402:B-Lymphocytes / Q000528:radiation effects; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects; D006019:Glycolysis / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000528:radiation effects*; D010085:Oxidative Phosphorylation / Q000528:radiation effects
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit