Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons

Jae Young Koh, Dae Kyong Kim, Jee Yeon Hwang, Yang Hee Kim, Ji Heui Seo

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Riluzole is used clinically in patients with amyotrophic lateral sclerosis. As oxidative stress, in addition to excitotoxicity, may be a major mechanism of motoneuron degeneration in patients with amyotrophic lateral sclerosis, we examined whether riluzole protects against nonexcitotoxic oxidative injury. Probably reflecting its weak antiexcitotoxic effects, riluzole (1-30 μM) attenuated submaximal neuronal death induced by 24-h exposure to 30 μM kainate or NMDA, but not that by 100 μM NMDA, in cortical cultures. Riluzole also attenuated nonexcitotoxic oxidative injury induced by exposure to FeCl3 in the presence of MK-801 and CNQX. Consistent with its antioxidative effects, riluzole reduced Fe3+-induced lipid peroxidation, and inhibited cytosolic phospholipase A2. By contrast, riluzole did not attenuate neuronal apoptosis induced by staurosporine. Rather unexpectedly, 24-48-h exposure to 100-300 μM riluzole induced neuronal death accompanied by nuclear and DNA fragmentations, which was attenuated by caspase inhibitor carbobenzyloxy-Val-Ala-Asp-fluoromethyl ketone but not by protein synthesis inhibitor cycloheximide. The present study demonstrates that riluzole has direct antioxidative actions, perhaps in part by inhibiting phospholipase A2. However, in the same neurons, riluzole paradoxically induces neuronal apoptosis in a caspase-sensitive manner. Considering current clinical use of riluzole, further studies are warranted to investigate its potential cytolethal effects.

Original languageEnglish (US)
Pages (from-to)716-723
Number of pages8
JournalJournal of Neurochemistry
Volume72
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Riluzole
Neurons
Amyotrophic Lateral Sclerosis
N-Methylaspartate
Cytosolic Phospholipases A2
Apoptosis
6-Cyano-7-nitroquinoxaline-2,3-dione
Protein Synthesis Inhibitors
Caspase Inhibitors
Oxidative stress
Dizocilpine Maleate
Staurosporine
Kainic Acid
Phospholipases A2
Wounds and Injuries
Motor Neurons
DNA Fragmentation
Cycloheximide
Caspases
Ketones

Keywords

  • Amyotrophic lateral sclerosis
  • Arachidonic acid
  • Caspase
  • Neuronal death
  • Phospholipase A

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons. / Koh, Jae Young; Kim, Dae Kyong; Hwang, Jee Yeon; Kim, Yang Hee; Seo, Ji Heui.

In: Journal of Neurochemistry, Vol. 72, No. 2, 1999, p. 716-723.

Research output: Contribution to journalArticle

Koh, Jae Young ; Kim, Dae Kyong ; Hwang, Jee Yeon ; Kim, Yang Hee ; Seo, Ji Heui. / Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons. In: Journal of Neurochemistry. 1999 ; Vol. 72, No. 2. pp. 716-723.
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