Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-18
pubmed:abstractText
Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen species production in mitochondria. We performed a detailed study of brain injury, including regional and cellular distribution of UCP2 mRNA, as well as measures of oxidative stress markers following permanent middle cerebral artery occlusion in UCP2 knockout (KO) and wild-type (WT) mice. Three days post ischemia, there was a massive induction of UCP2 mRNA confined to microglia in the peri-infarct area of WT mice. KO mice were less sensitive to ischemia as assessed by reduced brain infarct size, decreased densities of deoxyuridine triphosphate nick end-labelling (TUNEL)-labelled cells in the peri-infact area and lower levels of lipid peroxidation compared with WT mice. This resistance may be related to the substantial increase of basal manganese superoxide dismutase levels in neurons of KO mice. Importantly, we found a specific decrease of mitochondrial glutathione (GSH) levels in UCP2 expressing microglia of WT, but not in KO mice after ischemia. This specific association between UCP2 and mitochondrial GSH levels regulation was further confirmed using lipopolysaccharide models of peripheral inflammation, and in purified peritoneal macrophages. Moreover, our data imply that UCP2 is not directly involved in the regulation of ROS production but acts by regulating mitochondrial GSH levels in microglia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1283-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15147521-Animals, pubmed-meshheading:15147521-Antioxidants, pubmed-meshheading:15147521-Brain Ischemia, pubmed-meshheading:15147521-Cell Count, pubmed-meshheading:15147521-Cytochromes c, pubmed-meshheading:15147521-Disease Models, Animal, pubmed-meshheading:15147521-Genetic Predisposition to Disease, pubmed-meshheading:15147521-Glutathione, pubmed-meshheading:15147521-In Situ Nick-End Labeling, pubmed-meshheading:15147521-Ion Channels, pubmed-meshheading:15147521-Lipopolysaccharides, pubmed-meshheading:15147521-Macrophages, Peritoneal, pubmed-meshheading:15147521-Male, pubmed-meshheading:15147521-Membrane Transport Proteins, pubmed-meshheading:15147521-Mice, pubmed-meshheading:15147521-Mice, Knockout, pubmed-meshheading:15147521-Microglia, pubmed-meshheading:15147521-Mitochondria, pubmed-meshheading:15147521-Mitochondrial Proteins, pubmed-meshheading:15147521-Oxidative Stress, pubmed-meshheading:15147521-Protein Transport, pubmed-meshheading:15147521-RNA, Messenger, pubmed-meshheading:15147521-Superoxide Dismutase
pubmed:year
2004
pubmed:articleTitle
Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels.
pubmed:affiliation
Department of Psychiatry, University Hospitals Geneva, Geneva, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't