RGD Reference Report - Peroxisome proliferator-activated receptors gamma/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus. - Rat Genome Database

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Peroxisome proliferator-activated receptors gamma/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus.

Authors: Chuang, YC  Lin, TK  Huang, HY  Chang, WN  Liou, CW  Chen, SD  Chang, AY  Chan, SH 
Citation: Chuang YC, etal., J Neuroinflammation. 2012 Jul 31;9:184.
RGD ID: 10054246
Pubmed: PMID:22849356   (View Abstract at PubMed)
PMCID: PMC3444895   (View Article at PubMed Central)
DOI: DOI:10.1186/1742-2094-9-184   (Journal Full-text)

BACKGROUND: Status epilepticus induces subcellular changes that may lead to neuronal cell death in the hippocampus. However, the mechanism of seizure-induced neuronal cell death remains unclear. The mitochondrial uncoupling protein 2 (UCP2) is expressed in selected regions of the brain and is emerged as an endogenous neuroprotective molecule in many neurological disorders. We evaluated the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal cell death under experimental status epilepticus. METHODS: In Sprague-Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Oxidized protein level, translocation of Bcl-2, Bax and cytochrome c between cytosol and mitochondria, and expression of peroxisome proliferator-activated receptors gamma (PPARgamma) and UCP2 were examined in the hippocampal CA3 subfield following KA-induced status epilepticus. The effects of microinjection bilaterally into CA3 area of a PPARgamma agonist, rosiglitazone or a PPARgamma antagonist, GW9662 on UCP2 expression, induced superoxide anion (O(.2)(-)) production, oxidized protein level, mitochondrial respiratory chain enzyme activities, translocation of Bcl-2, Bax and cytochrome c, and DNA fragmentation in bilateral CA3 subfields were examined. RESULTS: Increased oxidized proteins and mitochondrial or cytosol translocation of Bax or cytochrome c in the hippocampal CA3 subfield was observed 3-48 h after experimental status epilepticus. Expression of PPARgamma and UCP2 increased 12-48 h after KA-induced status epilepticus. Pretreatment with rosiglitazone increased UCP2 expression, reduced protein oxidation, O(.2)(-) overproduction and dysfunction of mitochondrial Complex I, hindered the translocation of Bax and cytochrome c, and reduced DNA fragmentation in the CA3 subfield. Pretreatment with GW9662 produced opposite effects. CONCLUSIONS: Activation of PPARgamma upregulated mitochondrial UCP2 expression, which decreased overproduction of reactive oxygen species, improved mitochondrial Complex I dysfunction, inhibited mitochondrial translocation of Bax and prevented cytosolic release of cytochrome c by stabilizing the mitochondrial transmembrane potential, leading to amelioration of apoptotic neuronal cell death in the hippocampus following status epilepticus.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus treatmentISOBax (Rattus norvegicus)10054246; 10054246 RGD 
status epilepticus treatmentIEP 10054246 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)

Genes (Mus musculus)
Bax  (BCL2-associated X protein)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator)


Additional Information