Abstract:
:Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing human UCP-2, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced. In cultured cortical neurons, UCP-2 reduced cell death and inhibited caspase-3 activation induced by oxygen and glucose deprivation. Mild mitochondrial uncoupling by 2,4-dinitrophenol (DNP) reduced neuronal death, and UCP-2 activity was enhanced by palmitic acid in isolated mitochondria. Also in isolated mitochondria, UCP-2 shifted the release of reactive oxygen species from the mitochondrial matrix to the extramitochondrial space. We propose that UCP-2 is an inducible protein that is neuroprotective by activating cellular redox signaling or by inducing mild mitochondrial uncoupling that prevents the release of apoptogenic proteins.
journal_name
Nat Medjournal_title
Nature medicineauthors
Mattiasson G,Shamloo M,Gido G,Mathi K,Tomasevic G,Yi S,Warden CH,Castilho RF,Melcher T,Gonzalez-Zulueta M,Nikolich K,Wieloch Tdoi
10.1038/nm903keywords:
subject
Has Abstractpub_date
2003-08-01 00:00:00pages
1062-8issue
8eissn
1078-8956issn
1546-170Xpii
nm903journal_volume
9pub_type
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