PMID:22292025

Citation	Deng, S, Yang, Y, Han, Y, Li, X, Wang, X, Li, X, Zhang, Z and Wang, Y (2012) UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic conditions. PLoS ONE 7:e30714
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.
Links	PubMed PMC3265501 Online version:10.1371/journal.pone.0030714
Keywords	Adenocarcinoma/genetics; Adenocarcinoma/metabolism; Adenocarcinoma/pathology; Apoptosis/drug effects; Apoptosis/genetics; Cell Hypoxia/drug effects; Cell Hypoxia/genetics; Cell Hypoxia/physiology; Cell Line, Tumor; Cobalt/pharmacology; Down-Regulation/drug effects; Down-Regulation/genetics; Gene Expression; Gene Knockdown Techniques; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/genetics; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Ion Channels/antagonists & inhibitors; Ion Channels/genetics; Ion Channels/physiology; Lung Neoplasms/genetics; Lung Neoplasms/metabolism; Lung Neoplasms/pathology; Mitochondrial Proteins/antagonists & inhibitors; Mitochondrial Proteins/genetics; Mitochondrial Proteins/physiology; Oxygen/pharmacology; RNA, Small Interfering/pharmacology; Reactive Oxygen Species/metabolism; Reactive Oxygen Species/pharmacology; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HIF1A		GO:0001666: response to hypoxia	ECO:0000314:		P		Fig 1A as hypoxia occurs, levels of HIF-1alpha increase	complete CACAO 3761
HUMAN:UCP2		GO:0001666: response to hypoxia	ECO:0000314:		P		Fig 1B - UCP2 levels increase as levels of hypoxia increase	complete CACAO 3759
HUMAN:UCP2		GO:0006915: apoptotic process	ECO:0000314:		P		Fig 3A overexpression of UCP2 under hypoxic conditions decreases levels of apoptosis	complete CACAO 3760
HUMAN:UCP2	involved_in	GO:0001666: response to hypoxia	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

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