Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.
1-methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Salvianic acid A (SA), isolated from the Chinese herbal medicine Salvia miltiorrhiza, is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the protective effects of SA on MPP(+)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Treatment of SH-SY5Y cells with MPP(+) caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, the increase in Bax/Bcl-2 ratio, and the activation of caspase-3. MPP(+) induced mitochondria dysfunction characterized by mitochondrial membrane potential loss and cytochrome c release. These phenotypes induced by MPP(+) were reversed by SA. Our results suggested that the protective effects of SA on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties and anti-apoptotic activity via regulating the expression of Bcl-2 and Bax. These data indicated that SA might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.
Wang
Xin-Jian
XJ
Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Xu
Jian-Xing
JX
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D015153:Blotting, Western / Q000379:methods; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004226:Dithioerythritol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007773:Lactates / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D002109:Caffeic Acids; D007773:Lactates; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013439:Sulfhydryl Reagents; D051028:bcl-2-Associated X Protein; C066201:salvianolic acid A; D004226:Dithioerythritol; D045304:Cytochromes c; D002374:Catalase; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D006690:Bisbenzimidazole; D015655:1-Methyl-4-phenylpyridinium