A20 is up-regulated in primary mouse hepatocytes subjected to hypoxia and reperfusion.
Hepatic ischemia reperfusion-induced injury is a major medical concern, and it is important to characterize the adaptive mechanisms of hepatocytes to hypoxia and reoxygenation to sustain liver function. In this study, we reported a proteomic analysis of ischemia reperfusion-induced global responses in primary hepatocytes. The primary hepatocytes were isolated from mice and exposed to oxygen to mimic ischemia reperfusion. Total proteins were extracted from the cells and analyzed by two-dimensional gel electrophoresis followed by matrix-assisted laser desorption time-of-flight mass spectrometry. Zinc finger protein A20, mercaptopyruvate sulfur transferase, apolipoprotein E precursor and carbamoyl-phosphate synthase mitochondrial precursor were identified as differentially expressed in differently exposed groups. Reverse transcriptase polymerase chain reaction and Western blot analysis validated that A20 was significantly up-regulated in the hepatocytes subjected to hypoxia and reperfusion. In addition, the expression of peroxisome proliferator-activated receptor α, an A20 target, was up-regulated in the hepatocytes subjected to hypoxia and reperfusion. Our results on A20 provide new insight into the mechanism underlying the adaptation of hepatocytes to hypoxia and reperfusion. Because of its role in the up-regulation of peroxisome proliferator-activated receptor α expression to protect hepatocytes from reperfusion-induced apoptosis, A20 is a potential target for the prevention and therapy of liver injury after ischemia reperfusion.
Department of Pathophysiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Jiao
J
Sun
Luning
L
Sun
Ning
N
Zhang
Xiaomei
X
Lu
Haipeng
H
Zhang
D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D047493:PPAR alpha / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015427:Reperfusion Injury / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D047493:PPAR alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse; D010100:Oxygen