Anti-apoptotic effect of esculin on dopamine-induced cytotoxicity in the human neuroblastoma SH-SY5Y cell line.
Dopamine (DA), as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. In this study, we examined the effect of esculin, which was extracted from Fraxinus sielboldiana blume, on DA-induced cytotoxicity and the underlying mechanism in human neuroblastoma SH-SY5Y cells. Our results suggest that the protective effects of esculin (10(-7), 10(-6) and 10(-5) M) on DA-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level, and its anti-apoptotic effect via protecting mitochondrion membrane potential (DeltaPsim), enhancing superoxide dismutaese (SOD) activity and reduced glutathione (GSH) levels, and regulating P53, Bax and Bcl-2 expression. In addition, esculin inhibited the release of cytochrome c and apoptosis-inducing factor (AIF), and the protein expression of activated caspase 3. These data indicate that esculin may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease (PD).
Zhao
Da-Long
DL
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine affiliated Ministry of Education, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, District Xuanwu, Beijing, China.
Zou
Li-Bo
LB
Lin
Sheng
S
Shi
Jian-Gong
JG
Zhu
Hai-Bo
HB
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004929:Esculin / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics
D018492:Dopamine Antagonists; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004929:Esculin; D045304:Cytochromes c; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; D004298:Dopamine