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

Gustav Mattiasson, Mehrdad Shamloo, Gunilla Gido, Kavitha Mathi, Gregor Tomasevic, Saili Yi, Craig H Warden, Roger F. Castilho, Thorsten Melcher, Mirella Gonzalez-Zulueta, Karoly Nikolich, Tadeusz Wieloch

Research output: Contribution to journalArticle

394 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1062-1068
Number of pages7
JournalNature Medicine
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Brain Death
Brain
Mitochondria
Stroke
2,4-Dinitrophenol
Palmitic Acid
Thermogenesis
Oligonucleotide Array Sequence Analysis
Caspase 3
Enhanced recovery
Oxidation-Reduction
Organism Cloning
Reactive Oxygen Species
Proteins
Cell Death
Cloning
Cell death
Oxygen
Neurons
Glucose

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mattiasson, G., Shamloo, M., Gido, G., Mathi, K., Tomasevic, G., Yi, S., ... Wieloch, T. (2003). Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nature Medicine, 9(8), 1062-1068. https://doi.org/10.1038/nm903

Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. / Mattiasson, Gustav; Shamloo, Mehrdad; Gido, Gunilla; Mathi, Kavitha; Tomasevic, Gregor; Yi, Saili; Warden, Craig H; Castilho, Roger F.; Melcher, Thorsten; Gonzalez-Zulueta, Mirella; Nikolich, Karoly; Wieloch, Tadeusz.

In: Nature Medicine, Vol. 9, No. 8, 01.08.2003, p. 1062-1068.

Research output: Contribution to journalArticle

Mattiasson, G, Shamloo, M, Gido, G, Mathi, K, Tomasevic, G, Yi, S, Warden, CH, Castilho, RF, Melcher, T, Gonzalez-Zulueta, M, Nikolich, K & Wieloch, T 2003, 'Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma', Nature Medicine, vol. 9, no. 8, pp. 1062-1068. https://doi.org/10.1038/nm903
Mattiasson, Gustav ; Shamloo, Mehrdad ; Gido, Gunilla ; Mathi, Kavitha ; Tomasevic, Gregor ; Yi, Saili ; Warden, Craig H ; Castilho, Roger F. ; Melcher, Thorsten ; Gonzalez-Zulueta, Mirella ; Nikolich, Karoly ; Wieloch, Tadeusz. / Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. In: Nature Medicine. 2003 ; Vol. 9, No. 8. pp. 1062-1068.
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