Abstract
The Crosstalk between a tumor and its hypoxic microenvironment has become increasingly important. However, the exact role of UCP2 function in cancer cells under hypoxia remains unknown. In this study, UCP2 showed anti-apoptotic properties in A549 cells under hypoxic conditions. Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS) accumulation (P<0.001) and apoptosis (P<0.001) compared to the controls when the cells were exposed to hypoxia. Moreover, over-expression of UCP2 inhibited the release of cytochrome C and reduced the activation of caspase-9. Conversely, suppression of UCP2 resulted in the ROS generation (P = 0.006), the induction of apoptosis (P<0.001), and the release of cytochrome C from mitochondria to the cytosolic fraction, thus activating caspase-9. These data suggest that over-expression of UCP2 has anti-apoptotic properties by inhibiting ROS-mediated apoptosis in A549 cells under hypoxic conditions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma of Lung
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Apoptosis / drug effects*
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Apoptosis / genetics
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Cell Hypoxia / drug effects
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Cell Hypoxia / genetics
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Cell Hypoxia / physiology
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Cell Line, Tumor
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Cobalt / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Gene Expression
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Gene Knockdown Techniques
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Ion Channels / antagonists & inhibitors
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Ion Channels / genetics
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Ion Channels / physiology*
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mitochondrial Proteins / antagonists & inhibitors
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / physiology*
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Oxygen / pharmacology*
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RNA, Small Interfering / pharmacology
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Reactive Oxygen Species / metabolism
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Reactive Oxygen Species / pharmacology*
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Transfection
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Uncoupling Protein 2
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Ion Channels
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Mitochondrial Proteins
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RNA, Small Interfering
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Reactive Oxygen Species
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UCP2 protein, human
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Uncoupling Protein 2
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Cobalt
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cobaltous chloride
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Oxygen