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Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation.
Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2012 Feb 01; Vol. 302 (3), pp. G336-42. Date of Electronic Publication: 2011 Nov 17. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Cell Death drug effects
Cell Survival drug effects
Cells, Cultured
Emulsions pharmacology
Fatty Acids metabolism
Hepatocytes drug effects
Hepatocytes metabolism
Ion Channels genetics
Ion Channels metabolism
Lipid Peroxidation drug effects
Membrane Potential, Mitochondrial drug effects
Mice
Mice, Inbred Strains
Mice, Knockout
Mice, Obese
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Phospholipids pharmacology
Soybean Oil pharmacology
Uncoupling Protein 2
Cell Hypoxia physiology
Fatty Liver
Hepatocytes pathology
Ion Channels deficiency
Mitochondrial Proteins deficiency
Oxygen pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 302
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22094601
- Full Text :
- https://doi.org/10.1152/ajpgi.00049.2011