cytochrome-c-t and fraxetin

Fraxetin belongs to an extensive group of natural phenolic anti-oxidants. In the present study, using a human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on rotenone-mediated cytoxicity. Incubation of cells with the fraxetin led to a significant elevation dose-dependent of cellular GSH and this was accompanied by a marked protection against rotenone-mediated toxicity, which was also significantly reversed in the cells with buthionine sulfoximine (BSO) co-treatment. Taken together, this study suggested that intracellular GSH appeared to be an important factor in fraxetin-mediated cytoprotection against rotenone-toxicity in SH-SY5Y cells. Fraxetin at 10-100 muM inhibited the formation of ROS, cytochrome c release, activation of caspase-3 and 9, and suppressed the up-regulation of Bax, whereas no significant change occurred in Bcl-2 levels. Our results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against rotenone-induced cytotoxicity.

Topics: Apoptosis; Blotting, Western; Caspases; Cell Count; Cell Line, Tumor; Cell Survival; Coumarins; Cytochromes c; Dose-Response Relationship, Drug; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Glutathione; Humans; Insecticides; Mitochondria; Neuroblastoma; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Rotenone