Effect of ionizing radiation on liver protein oxidation and metabolic function in C57BL/6J mice

Abstract

Purpose: 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.

Materials and 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.

Keywords: Protein damage; protein biochemistry; radiosensitivity.