Document Detail


Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation.
MedLine Citation:
PMID:  22094601     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation.
Authors:
Zachary P Evans; Arun P Palanisamy; Alton G Sutter; Justin D Ellett; Venkat K Ramshesh; Hubert Attaway; Michael G Schmidt; Rick G Schnellmann; Kenneth D Chavin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-17
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  302     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-04-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G336-42     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Cell Death / drug effects
Cell Hypoxia / physiology*
Cell Survival / drug effects
Cells, Cultured
Emulsions / pharmacology
Fatty Acids / metabolism
Fatty Liver*
Hepatocytes / drug effects,  metabolism,  pathology*
Ion Channels / deficiency*,  genetics,  metabolism
Lipid Peroxidation / drug effects
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Inbred Strains
Mice, Knockout
Mice, Obese
Mitochondrial Proteins / deficiency*,  genetics,  metabolism
Oxygen / pharmacology*
Phospholipids / pharmacology
Soybean Oil / pharmacology
Grant Support
ID/Acronym/Agency:
DK069369/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Emulsions; 0/Fatty Acids; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Phospholipids; 0/mitochondrial uncoupling protein 2; 0/soybean oil, phospholipid emulsion; 56-65-5/Adenosine Triphosphate; 7782-44-7/Oxygen; 8001-22-7/Soybean Oil
Comments/Corrections

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