期刊
JOURNAL OF SURGICAL RESEARCH
卷 141, 期 2, 页码 234-240出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2006.12.554
关键词
ischemia-reperfusion; ATP; apoptosis; mitochondrial calcium; purinergic receptor; liver preservation
类别
资金
- NCI NIH HHS [T32 CA009592] Funding Source: Medline
- NIDDK NIH HHS [K08 DK061768-05, R01 DK064669, DK064669, T32 DK007673, R01 DK064669-01A2, T32 DK07673, DK59390-1] Funding Source: Medline
Background. Purinergic (P2Y) receptors play an important role in intracellular Ca2+ regulation in hepatocytes. Prevention of mitochondrial Ca2+ (mCa(2+)) overload during ischemic conditions prevents cellular cell death during the early reperfusion period. P2Y antagonists are cytoprotective in other settings. We studied the effect of P2Y receptor antagonism on mitochondrial associated cell death during the period of cold storage. Methods. HepG2 cells were stored in UW with or without 300 mu M reactive blue 2 (RB2) or 10 mu M ruthenium red (RR) under either normoxic-hypothermic or hypoxic-hypothermic conditions. Cytoplasmic cytochrome c levels were studied by transfection of cytochrome c-GFP. Immunofluorescence determined the intracellular, spatio-temporal distribution of Bax, and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to evaluate cell death. Intracellular compartmental ATP levels were assayed by transfecting with luciferase vectors specific for cytoplasm (PcDNA3-luciferase-LL/V) and mitochondria (PcDNA3-COX8-luciferase). Results. Bax translocation to the mitochondria occurred immediately following cold storage and was followed by cytochrome c-GFP redistribution to the cytosol during rewarming. RB2 treatment significantly attenuated Bax translocation, cytochrome c-GFP redistribution, and cell death following both storage conditions. Both RR and RB2 provided cytoprotection despite ongoing cytoplasmic ATP consumption during cold ischemia. Conclusion. These data indicate that the cytoprotective effects of mCa(2+) uptake inhibition and P2Y receptor antagonism are independent of cytoplasmic ATP levels during cold ischemia. (c) 2007 Elsevier Inc. All rights reserved.
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