title: Effect of ionizing radiation on liver protein oxidation and metabolic function in C57BL/6J mice.
abstract: OBJECTIVE
  Protein oxidation in response to radiation results in DNA damage, endoplasmic reticulum stress/unfolded protein response, cell cycle arrest, cell death and senescence. The liver, a relatively radiosensitive organ, undergoes measurable alterations in metabolic functions following irradiation. Accordingly, we investigated radiation-induced changes in liver metabolism and alterations in protein oxidation.
  
  
  METHODS
  C57BL/6 mice were sham irradiated or exposed to 8.5 Gy (60)Co (0.6 Gy/min) total body irradiation. Metabolites and metabolic enzymes in the blood and liver tissue were analyzed. Two-dimensional gel electrophoresis and OxyBlot™ were used to detect carbonylated proteins that were then identified by peptide mass fingerprinting.
  
  
  RESULTS
  Analysis of serum metabolites revealed elevated glucose, bilirubin, lactate dehydrogenase (LDH), high-density lipoprotein, and aspartate aminotransferase within 24-72 h post irradiation. Liver tissue LDH and alkaline phosphatase activities were elevated 24-72 h post irradiation. OxyBlotting revealed that the hepatic proteome contains baseline protein carbonylation. Radiation exposure increased carbonylation of specific liver proteins including carbonic anhydrase 1, α-enolase, and regucalcin.
  
  
  CONCLUSIONS
  8.5 Gy irradiation resulted in distinct metabolic alterations in hepatic functions. Coincident with these changes, radiation induced the carbonylation of specific liver enzymes. The oxidation of liver enzymes may underlie some radiation-induced alterations in hepatic function.
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Barshishat-Kupper
authors.forename: Ashlee J
authors.initials: AJ
authors.lastname: Tipton
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: McCart
authors.forename: Jeffrey
authors.initials: J
authors.lastname: McCue
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mueller
authors.forename: Regina M
authors.initials: RM
authors.lastname: Day
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000528:radiation effects; D050050:Protein Carbonylation / Q000528:radiation effects; D011506:Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D011506:Proteins
keywords: Protein damage; protein biochemistry; radiosensitivity