Effect of JGK-263 as a new glycogen synthase kinase-3 beta inhibitor on extrinsic apoptosis pathway in motor neuronal cells
- Title
- Effect of JGK-263 as a new glycogen synthase kinase-3 beta inhibitor on extrinsic apoptosis pathway in motor neuronal cells
- Author
- 김승현
- Keywords
- Glycogen synthase kinase-3; JGK-263; Extrinsic apoptosis; Motor neuron; Amyotrophic lateral sclerosis
- Issue Date
- 2013-09
- Publisher
- Elsevier Science B.V., Amsterdam
- Citation
- Biochemical and Biophysical Research Communications, Volume 439, Issue 2, 309-314
- Abstract
- Glycogen synthase kinase-3β (GSK-3β) has been identified as one of the important pathogenic mechanisms in motor neuronal death. GSK-3β inhibitor has been investigated as a modulator of apoptosis and has been shown to confer significant protective effects on cell death in neurodegenerative diseases. However, GSK-3β is known to have paradoxical effects on apoptosis subtypes, i.e., pro-apoptotic in mitochondrial-associated intrinsic apoptosis, but anti-apoptotic in death receptor-related extrinsic apoptosis. In this study, we evaluated the effect of a new GSK-3β inhibitor (JGK-263) on motor neuron cell survival and apoptosis, by using low to high doses of JGK-263 after 48h of serum withdrawal, and monitoring changes in extrinsic apoptosis pathway components, including Fas, FasL, cleaved caspase-8, p38α, and the Fas-Daxx interaction. Cell survival peaked after treatment of serum-deprived cells with 50μM JGK-263. The present study showed that treatment with JGK-263 reduced serum-deprivation-induced motor neuronal apoptosis by inactivating not only the intrinsic, but also the extrinsic apoptosis pathway. These results suggest that JGK-263 has a neuroprotective effect through effective modulation of the extrinsic apoptosis pathway in motor neuron degeneration.
- URI
- https://www.sciencedirect.com/science/article/pii/S0006291X13012424?via%3Dihubhttp://hdl.handle.net/20.500.11754/45979
- ISSN
- 0006-291X; 1090-2104
- DOI
- 10.1016/j.bbrc.2013.07.080
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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