| Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation. | |
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MedLine Citation:
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PMID: 22094601 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-11-17 |
Journal Detail:
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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:
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Created Date: 2012-01-25 Completed Date: 2012-04-23 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G336-42 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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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:
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DK069369/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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