Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons
- Authors
- Koh, JY; Kim, DK; Hwang, JY; Kim, YH; Seo, JH
- Issue Date
- Feb-1999
- Publisher
- WILEY
- Keywords
- amyotrophic lateral sclerosis; neuronal death; phospholipase A(2); arachidonic acid caspase
- Citation
- JOURNAL OF NEUROCHEMISTRY, v.72, no.2, pp 716 - 723
- Pages
- 8
- Journal Title
- JOURNAL OF NEUROCHEMISTRY
- Volume
- 72
- Number
- 2
- Start Page
- 716
- End Page
- 723
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/25428
- DOI
- 10.1046/j.1471-4159.1999.0720716.x
- ISSN
- 0022-3042
1471-4159
- 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 mu M) attenuated submaximal neuronal death induced by 24-h exposure to 30 mu M kainate or NMDA, but not that by 100 mu M 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 A(2). By contrast, riluzole did not attenuate neuronal apoptosis induced by staurosporine. Rather unexpectedly, 24-48-h exposure to 100-300 mu M 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 A(2). 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.
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