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Publication : Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning.

First Author  Diano S Year  2003
Journal  Endocrinology Volume  144
Issue  11 Pages  5014-21
PubMed ID  12960023 Mgi Jnum  J:87233
Mgi Id  MGI:2683948 Doi  10.1210/en.2003-0667
Citation  Diano S, et al. (2003) Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning. Endocrinology 144(11):5014-21
abstractText  The mitochondrial uncoupling protein (UCP2) is expressed in selected regions of the brain. Here we demonstrate that up-regulation of UCP2 is part of a neuroprotective set of responses to various cellular stresses in vitro and in vivo. PC12 cells, when transfected with UCP2, were protected against free radical-induced cell death. Seizure activity was associated with elevated UCP2 levels and mitochondrial uncoupling activity. In transgenic mice that expressed UCP2 constitutively in the hippocampus before seizure induction, a robust reduction in cell death was seen. Because UCP2 increased mitochondrial number and ATP levels with a parallel decrease in free radical-induced damage, it is reasonable to suggest that mitochondrial UCPs precondition neurons by dissociating cellular energy production from that of free radicals to withstand the harmful effects of cellular stress occurring in a variety of neurodegenerative disorders, including epilepsy.
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