J Korean Neurol Assoc > Volume 22(4); 2004 > Article
Journal of the Korean Neurological Association 2004;22(4): 375-381.
산화성 손상을 받은 PC12 세포에서 Diallyl Disulfide에 의한 Cytochrome c 매개성 아팝토시스 차단 효과
고성호, 권혁성† 박윤주† 김준규† 김기석† 송치원† 김주환† 김주한* 김명호* 김경숙‡ 유현정§ 정해관† 김승현*‡
한양대학교 의과대학 신경과학교실*, 정신건강연구소‡, 식품의약품안전청 국립독성연구원 일반독성부 신경독성과†, 분당제생병원 신경과§
Diallyl Disulfide Inhibits Cytochrome c-Mediated Apoptosis in H2O2 Induced Death of Neuronal-differentiated PC12 Cells
Seong-Ho Koh
Department of Neurology* and Institute of Mental Health‡, College of Medicine, Hanyang University, Seoul; Department of General Toxicology, National Institute of Toxicological Research, KFDA†, Seoul; Department of Neurology, Bundang Jesaeng Hospital§, Gyeonggi, Korea
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.Key Words: Diallyl disulfide, Antioxidant, Apoptosis, Caspase-3, PARP


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