Ectopic Expression of the Catalytic Subunit of Telomerase Protects against Brain Injury Resulting from Ischemia and NMDA-Induced Neurotoxicity

Hyo Jung Kang, Yoon Sik Choi, Seung Beom Hong, Kee Won Kim, Ran Sook Woo, Seok Joon Won, Eun Ju Kim, Hee Kyung Jeon, So Young Jo, Tae Kook Kim, Robert Bachoo, Ian J. Reynolds, Byoung Joo Gwag, Han Woong Lee

Research output: Contribution to journalArticle

115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1280-1287
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number6
DOIs
StatePublished - Feb 11 2004

Keywords

  • Calcium
  • Catalytic subunit of telomerase
  • Excitotoxicity
  • Ischemia
  • Mitochondria
  • NMDA

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kang, H. J., Choi, Y. S., Hong, S. B., Kim, K. W., Woo, R. S., Won, S. J., Kim, E. J., Jeon, H. K., Jo, S. Y., Kim, T. K., Bachoo, R., Reynolds, I. J., Gwag, B. J., & Lee, H. W. (2004). Ectopic Expression of the Catalytic Subunit of Telomerase Protects against Brain Injury Resulting from Ischemia and NMDA-Induced Neurotoxicity. Journal of Neuroscience, 24(6), 1280-1287. https://doi.org/10.1523/JNEUROSCI.4082-03.2004