Inhibitory Effects Of Astaxanthin On Oxidative Stress-induced Cytotoxicity And The Underlined Mechamisms

In this study，we investigated the effects of astaxanthin (AST) on hydrogenperoxide-induced cell toxicity and the underlined molecular mechanisms in humanneuroblastoma SH-SY5Y cells. The cells were pre-incubated with AST (50ng/ml)for24h and then treated with500μM hydrogen peroxide. The effects of AST on cellviability and apoptosis were then determined. Cell signaling involved in apoptosisand cell survival such as the activities of caspase-3, the expression of Bcl-2familyproteins and the activation of Akt and CREB were also analyzed.The results showed that AST significantly inhibited the cell toxicity andapoptosis induced by hydrogen peroxide in SH-SY5Y cells. Hydrogen peroxidetreatment induced a significant decrease in GSH content while AST pretreatmentinhibited this depletion of GSH content, suggesting that AST could reduce theoxidative stress induced by hydrogen peroxide. Analyses of apoptotic signalingshowed a significant decrease of hydrogen peroxide-induced caspase-3activation byAST pretreatment. RT-PCR results showed that AST pretreatment inhibitedhydrogen peroxide-induced changes in the expression of Bcl-2family proteins,promoting the expression of antiapoptotic Bcl-2and Bcl-XL proteins whiledecreasing the expression of proapoptic Bak protein. Western blot results showedthat hydrogen peroxide increased the phosphorylation of Akt and CREB, while ASTpretreatment reduced hydrogen peroxide-induced phosphorylation of Akt and CREB.Interestingly, it was found that AST treatment itself also increased thephosphorylation of Akt and CREB. These results suggested that AST might inhibitcell toxicity and promote cell survival through regulating Akt/CREB pathways.In conclusion, AST inhibits hydrogen peroxide-induced cell toxicity andapoptosis through inhibition of hydrogen peroxide-induced apoptotic signaling andpromotion of cell survival pathway. The inhibitory effects of AST on hydrogenperoxide-induced cell toxicity may also be related to its antioxidant property.