Astaxanthin Protects Against MPP~+-induced Oxidative Stress In PC12Cells Via The HO-1/NOX2Axis

Background:PD is a high incidence of neurodegenerative diseases in elderly people,and oxidatie stress plays an important role in PD pathogenesis mechanism. Brain is ahigh oxygen metabolism rate tissue, and the balance of antioxidant and oxidant have aprotection to brain. In recent years, it found that astaxanthin plays an an importantrole in antiradical, antioxidation and antiapoptotic, and can through the blood brainbarrier smoothly. HO-1/NOX2cell signaling pathways was not been reported onMPP~~+-induced oxidative stress in PC12cells, whether ATX paly a protection role ofMPP~~+-induced oxidase stress in PC12cells, via the HO-1/NOX2axis.Objective:To elucidate Hemin(HO-1inducer) protect PC12cells againstMPP~~+-induced oxidative damage, to research whether by the relationship with HO-1and NOX2. To elucidate the the neuroprotection and molecμLar mechanisms ofAstaxanthin(ATX) on PC12cells.Methods:Well-differentiated PC12cells treated with MPP~~+were used as the in vitrocell model. A MTT assay was used to investigate the effects of MPP~~+, ATX, Hemin,DPI, and SnPPIX on PC12cell viability. Flow cytometry analysis was used to detectintracellμLar ROS production. Western blot analysis was used to observe theexpression of NOX2, HO-1and Nrf2. Immunofluorescent double staining wasperformed to examine the subcellμLar localization of the NOX2and HO-1, whilereal-time PCR was used to observe the expression of both NOX2and HO-1mRNAlevels.Res μ Lts:After the treat of MPP~~+, cell viability was significantly decreased.Respectively, ATX, SnPPIX, Hemin treated group cell viability have no significantdifferent. ATX decreasing NADPH oxidase-dependent intracellμLarROS-generation of MPP~~+-induced, which was a concentration-dependent. The proteinof NOX2, HO-1and Nrf2were increased by MPP~~+-induced(P<0.05), after Hemin andATX pretreated, the NOX2expression was decreased, Nrf2and HO-1expression were increased. The NOX2mRNA and HO-1mRNA were increased byMPP~+-induced (P<0.05), after Hemin and ATX pretreated, the NOX2mRNAexpression was decreased and HO-1mRNA expression were increased. MPP~+canenhance the fluorescence intensity of NOX2and HO-1, after Hemin and ATXpretreated, the fluorescence intensity of NOX2was reduced and HO-1was enhanced.Conclusions： Hemin can increase HO-1but inhibit NOX2expression, theover-expression of HO-1may suppress NOX2and ROS production of the NOX2dependents, then reduced oxidative damage induced by MPP~+. ATX suppressesMPP~+-induced oxidative stress in PC12cells via the HO-1/NOX2axis and reducingthe ROS production.