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KMID : 0359720040220040375
Journal of the Korean Neurological Association
2004 Volume.22 No. 4 p.375 ~ p.381
Diallyl Disulfide Inhibits Cytochrome c-Mediated Apoptosis in H2O2 Induced Death of Neuronal-differentiated PC12 Cells
Koh Seong-Ho

Kwon Hyug-Sung
Park Youn-Joo
Kim Jun-Gyou
Kim Ki-Sok
Song Chi-Won
Kim Ju-Hwan
Kim Ju-Han
Kim Myung-Ho
Kim Kyeong-Sook
Yu Hyun-Jeung
Jung Hai-Kwan
Kim Seung-Hyun
Abstract
Background: The effects of diallyl disulfide (DADS), a garlic derived compound, on the viability and cell signaling-like the downstream signaling through cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP) during an oxidative-stress induced injury were studied using H2O2 treated neuronal-differentiated PC12 cells by a nerve growth factor.

Methods: To evaluate the toxicity of the DADS itself, the viability of the differentiated PC12 cells treated with several concentrations of DADS was evaluated with 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. To evaluate the protective effect of the low concentration of DADS from oxidative stress, the viability of the cells (DADS pretreated vs. not pretreated) was evaluated following the exposure to 100 µM H2O2. Additionally, the expression of caspase-3, PARP, and cytochrome c was examined using western blot analyses.

Results: The viability was not affected at low concentrations of DADS, up to 20 µM, but, over this concentration, it was decreased. Compared with the cells treated with only 100 µM H2O2, the pretreatment with low concentrations of DADS before exposure to 100 µM H2O2 increased the viability and induced the inhibition of caspase-3 activation, PARP cleavage, and cytochrome c release.

Conclusions: These results show that low concentrations of DADS shows neuroprotective effects by affecting the downstream signaling through cytochrome c, caspase-3, and PARP pathway and may be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.
KEYWORD
Diallyl disulfide, Antioxidant, Apoptosis, Caspase-3, PARP
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