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Ectopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity.

Authors
Kang, HJ; Choi, YS; Hong, SB; Kim, KW; Woo, RS; Won, SJ; Kim, EJ; Jeon, HK; Jo, SY; Kim, TK; Bachoo, R; Reynolds, IJ; Gwag, BJ; Lee, HW
Citation
The Journal of neuroscience : the official journal of the Society for Neuroscience, 24(6):1280-1287, 2004
Journal Title
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN
0270-64741529-2401
Abstract
The catalytic subunit of telomerase reverse transcriptase (TERT) protects dividing cells from replicative senescence in vitro. Here, we show that expression of TERT mRNA is induced in the ipsilateral cortical neurons after occlusion of the middle cerebral artery in adult mice. Transgenic mice that overexpress TERT showed significant resistance to ischemic brain injury. Among excitotoxicity, oxidative stress, and apoptosis comprising of routes of ischemic neuronal death, NMDA receptor-mediated excitotoxicity was reduced in forebrain cell cultures overexpressing TERT. NMDA-induced accumulation of cytosolic free Ca2+ ([Ca2+]c) was reduced in forebrain neurons from TERT transgenic mice, which was attributable to the rapid flow of [Ca2+]c into the mitochondria from the cytosol without change in Ca2+ influx and efflux through the plasma membrane. The present study provides evidence that TERT is inducible in postmitotic neurons after ischemic brain injury and prevents NMDA neurotoxicity through shift of the cytosolic free Ca2+ into the mitochondria, and thus plays a protective role in ameliorating ischemic neuronal cell death.
MeSH terms
AnimalsBrain Injury, Chronic/chemically induced/genetics/*prevention & controlBrain Ischemia/genetics/*therapyCalcium/metabolismCells, CulturedCoculture TechniquesDNA-Binding ProteinsDisease Models, AnimalExcitatory Amino Acid AgonistsFluorescent DyesGene Expression RegulationHypoxia-Ischemia, Brain/metabolism/pathology/prevention & controlMembrane Potentials/drug effects/geneticsMiceMice, TransgenicMitochondria/drug effects/metabolism*N-MethylaspartateNeuroglia/cytologyNeurons/cytology/drug effects/metabolismNeurotoxicity Syndromes/etiology/*prevention & controlNeurotoxinsRNA, Messenger/biosynthesisTelomerase/*biosynthesis/genetics
DOI
10.1523/JNEUROSCI.4082-03.2004
PMID
14960598
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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