期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 6, 页码 1280-1287出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4082-03.2004
关键词
catalytic subunit of telomerase; ischemia; excitotoxicity; NMDA; calcium; mitochondria
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, NMDAreceptor-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.
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