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Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.

Mattiasson, Gustav LU ; Shamloo, Mehrdad ; Gidö, Gunilla LU ; Mathi, Kavitha ; Tomasevic, Gregor LU ; Yi, Saili ; Warden, Craig H. ; Castilho, Roger F. ; Melcher, Thorsten and Gonzalez-Zulueta, Mirella , et al. (2003) In Nature Medicine 9(8). p.1062-1068
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
9
issue
8
pages
1062 - 1068
publisher
Nature Publishing Group
external identifiers
  • pmid:12858170
  • wos:000184484900031
  • scopus:0041464712
ISSN
1546-170X
DOI
10.1038/nm903
language
English
LU publication?
yes
id
92ca7048-b5b6-4912-97ca-b6e572b944b0 (old id 116476)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12858170&dopt=Abstract
date added to LUP
2016-04-01 16:34:56
date last changed
2022-03-30 08:46:48
@article{92ca7048-b5b6-4912-97ca-b6e572b944b0,
  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.}},
  author       = {{Mattiasson, Gustav and Shamloo, Mehrdad and Gidö, Gunilla and Mathi, Kavitha and Tomasevic, Gregor and Yi, Saili and Warden, Craig H. and Castilho, Roger F. and Melcher, Thorsten and Gonzalez-Zulueta, Mirella and Nikolich, Karoly and Wieloch, Tadeusz}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1062--1068}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.}},
  url          = {{http://dx.doi.org/10.1038/nm903}},
  doi          = {{10.1038/nm903}},
  volume       = {{9}},
  year         = {{2003}},
}