Comparative analysis of the serum proteome for biomarker discovery to reveal hepatotoxicity induced by iron ion radiation in mice.
OBJECTIVE
Proteomic analysis of serum biomarkers to determine liver toxicity after exposure to cosmic radiation has not been performed previously. This study was to identify serum biomarkers associated with hepatotoxicity following exposure to iron ion radiation.


METHODS
Male mice were whole-body irradiated with a 2grayunit (Gy) iron ion beam, and after 3months, serum and liver samples were collected. Two-dimensional electrophoresis (2-DE) was used to separate the identified serum proteins, and matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-TOF-TOF) was performed to identify differentially expressed proteins. Enzyme-linked immunosorbent assays and immunoblotting were applied to evaluate protein expression, and immunohistochemistry and immunofluorescence were used to investigate protein localization. Real-time polymerase chain reaction (PCR) was performed to confirm altered gene expression.


RESULTS
A total of 11 spots that showed differential expression were screened and identified as seven proteins. Of these, six proteins were in the same bioinformatics network and included complement component 3, serum amyloid P-component, apolipoprotein E, alpha-2-macroglobulin, fibrinogen alpha chain, and fibrinogen gamma chain. All of these proteins are synthesized by the liver, and may play an important role in liver toxicity. We also confirmed the mRNA transcription, and found that mRNA expression of the six identified proteins increased in the liver in irradiated mice.


CONCLUSIONS
These results suggest that these proteins may be potential biomarkers of hepatotoxicity in astronauts enduring long space missions.
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China.
Hongyan
H
Li
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070,China.
Yuxuan
Y
He
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China.
Cuixia
C
Di
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Jiawei
J
Yan
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215021, China. Electronic address: zhangh@impcas.ac.cn.
Hong
H
Zhang
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D007477:Ions / Q000009:adverse effects; D007501:Iron / Q000009:adverse effects; D008099:Liver / Q000473:pathology* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods; D011832:Radiation Injuries / Q000097:blood* / Q000473:pathology; D011839:Radiation, Ionizing
D015415:Biomarkers; D001798:Blood Proteins; D007477:Ions; D020543:Proteome; D007501:Iron
Biomarker; Liver; Proteomics; Serum; Space radiation