Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis.
BACKGROUND
Oxidative damage plays a major part in the pathogenesis of liver disease. Uncoupling proteins (UCPs) may be able to limit the generation of reactive oxygen species (ROS) and be cytoprotective.


METHODS
We investigated the effect of up-regulation of UCP2 in a hepatoblastoma cell line exposed to menadione or hypoxia/re-oxygenation.


RESULTS
Lipid and protein oxidation was increased in HepG2 cells exposed to ROS but this increase was significantly lower in cells over-expressing UCP2 under identical conditions. LDH release increased 2.5-fold in response to hypoxia/re-oxygenation in control HepG2 cells with no significant increase in UCP2 transfected cells. Hypoxia/re-oxygenation resulted in a reduction in liver-specific protein secretion that was attenuated in transfected cells and UCP2 over-expression also resulted in a 66% reduction in apoptosis compared with non-transfected controls.


CONCLUSIONS
These data suggest that UCP2 can limit oxidative damage in HepG2 cells in response to oxidative stress resulting in improved cell function and resistance to apoptosis.
Centre for Hepatology, Department of Medicine, Royal Free and University College Medical School, London, UK. pcollins@rfc.ucl.ac.uk
Peter
P
Collins
Catherine
C
Jones
Sarah
S
Choudhury
Leonard
L
Damelin
Humphrey
H
Hodgson
D000933:Antifibrinolytic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007473:Ion Channels; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D026901:Membrane Transport Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D014162:Transfection; D014475:Uncoupling Agents / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D015854:Up-Regulation; D024483:Vitamin K 3 / Q000494:pharmacology
D000933:Antifibrinolytic Agents; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D024483:Vitamin K 3; D010100:Oxygen