Rosuvastatin induces delayed preconditioning against L-glutamate excitotoxicity in cultured cortical neurons

Ferenc Domoki, Béla Kis, Tamás Gáspár, James A. Snipes, Ferenc Bari, David W. Busija

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We tested whether rosuvastatin (RST) protected against excitotoxic neuronal cell death in rat primary cortical neuronal cultures. l-Glutamate (200μM, 1h) reduced neuronal viability (% of naive controls, mean±SEM, n=8-32, *p<0.05) from 100±2% to 60±1%*, but pretreatment with RST (0.5μM, 3 days) increased survival to 88±2%*. RST-induced neuroprotection was not affected by co-application with mevalonate (10μM), although the same dose of mevalonate fully prevented the neurotoxic effects of a high dose (20μM) of RST. RST (0.5μM) pretreatment did not affect mitochondrial membrane potential or superoxide anion levels in quiescent neurons. However, RST pretreatment blunted elevations in free intracellular Ca2+ and reduced increases in superoxide anion levels following glutamate exposure. Manganese superoxide dismutase (SOD), copper-zinc SOD, catalase, and reduced glutathione levels were unaffected by RST pretreatment. In contrast, acute, one time RST application did not affect either baseline or l-glutamate-induced increases in superoxide levels. In summary, three-day RST pretreatment induces resistance to the excitotoxic effect of l-glutamate in cultured neurons apparently by a mechanism that is independent of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition. The delayed neuroprotection by RST against excitotoxicity does not involve sustained mitochondrial depolarization or superoxide anion production as initiating events, although it is associated with reduced Ca2+ influx and superoxide anion production upon l-glutamate challenge.

Original languageEnglish
Pages (from-to)404-409
Number of pages6
JournalNeurochemistry international
Volume56
Issue number3
DOIs
Publication statusPublished - Feb 1 2010

Keywords

  • Cell culture
  • Intracellular calcium
  • Neuroprotection
  • Reactive oxygen species
  • Statins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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