Proteomic analysis of hepatic ischemia/reperfusion injury and ischemic preconditioning in mice revealed the protective role of ATP5beta.
Hepatic ischemia/reperfusion (I/R) injury is an inevitable consequence during liver surgery. Ischemic preconditioning (IPC) has been shown to protect the livers from I/R injury, partially mediated by preservation of hepatic ATP contents. However, the precise molecular mechanisms of these events remain poorly elucidated. In this study, liver proteomes of the mice subjected to I/R injury pretreated with or without IPC were analyzed using 2-DE combined with MALDI-TOF/TOF mass analysis. Twenty proteins showing more than 1.5-fold difference were identified in the livers upon I/R injury. Among these proteins, four proteins were further regulated by IPC when compared with nonpretreated controls. One of these proteins, ATP synthase beta subunit (ATP5beta) catalyzes the rate-limiting step of ATP formation. The expression level of ATP5beta, which was further validated by Western blot analysis, was significantly decreased upon I/R injury while turned over by IPC pretreatment. Change pattern of hepatic ATP corresponded with that of ATP5beta expression, indicating that increasing hepatic ATP5beta expression might be a reason for ATP-preserving effect of IPC. In summary, this study provided new clues for understanding the mechanisms of IPC against I/R injury. The protective role of ATP5beta might give evidences for developing new therapeutic approaches against hepatic I/R injury.
Xu
Chengfu
C
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Zhang
Xuequn
X
Yu
Chaohui
C
Lu
Guohua
G
Chen
Shaohua
S
Xu
Liming
L
Ding
Wei
W
Shi
Qiaojuan
Q
Li
Youming
Y
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000410:Alanine Transaminase / Q000032:analysis / Q000378:metabolism; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000502:physiology; D019194:Ischemic Preconditioning; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D025261:Mitochondrial Proton-Translocating ATPases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D040901:Proteomics; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology
D011506:Proteins; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C530489:ATP5b protein, mouse; D025261:Mitochondrial Proton-Translocating ATPases