The Neuroprotective Effect And Mechanismof Curcumin On Rotenone-induced Cell Model Of Parkinson Disease

Background and objectiveParkinson’s disease(Parkinson diseases,PD)is a kind of nervous system degenerative disease,its main pathological feature is the substantia nigra Dopamine(Dopamine,DA)neuronal cell death and the substantia nigra striatum pathway degradation.Because-the substantia nigra striatum pathways of exhausted,black epicuticular thalamus have obvious inhibitory effect on muscle movement and muscle tension control is abate,eventually appear static tremor,muscle rigidity and clinical symptoms such as slow.The present study showed that many factors such as oxidative stress,mitochondrial function injury,inflammation,proteasome dysfunction such as participate in the occurrence of PD,but the specific mechanism is not fully clear.Curcumin is the active components of turmeric,which has been widely used as a food spices and herbs.Curcumin is extracted from curcuma rhizome a phenolic pigment,has many pharmacological effects such as anti-inflammatory,antioxidant,scavenging free radicals.Studies have shown that curcumin can induce the expression of Bcl-2 to suppress the intracellular reactive oxygen species induced by MPP + tired material generated,so as to maintain the stability of the mitochondrial membrane potential,reduce the release of cytochrome C,the final against oxidative stress.At the same time of curcumin can increase the level of GSH,inhibit lipid peroxidation,protect the role of dopamine neurons.Lysine residues acetylated protein posttranslational modification and adjustment to play an important role,it is common in organisms.With the literature,there is more than 20% of the proteins in the mitochondria acetylated phenomenon.SirT3 is a kind of depends on the nicotinamide adenine dinucleotide(NAD)Ⅲclass to acetylation enzyme,mainly exist in the heart,brain,kidney and liver abundant fine body tissues and organs,is one of the members of the family of mechanisms.In recent years,people found that Sirt3 can to take off the mitochondrial protein acetylation acetylation to maintain normal physiological function of mitochondria,can effectively reduce oxidative stress load caused by the happening of the disease.And its mechanism may reduce oxidative stress damage by acetylation activation of transcription factors activate the fork box O subtribe 3 a(FOXO3a,forkhead box O 3 a)to increase ROS removal systems such as MnSOD and catalase catalase(CAT)expression.Previous experiments have confirmed that curcumin can regulate the expression of Sirt3 through to rotenone induced chronic PD protective SD rat model.Curcumin might by activating FOXO3 a Sirt3 activation and raised MnSOD and CAT expression to suppress the SH SY5 Y cells induced by rotenone damage or apoptosis,is one of this experimental research to explore the issue.Therefore,this study choose curcumin treatment induced by rotenone SH SY5 Y cell model,testing the cell vitality,ROS levels,SIRT3,FOXO3 a,Mn-SOD and CAT protein expression,to explore the protective effects of curcumin on PD cell model and curcumin,SIRT3,FOXO3 a relations with ROS removal system and its related mechanism mediated by provide theoretical basis for clinical treatment and new ideas.Materials and methods SH-SY5 Y cells model is established firstly,then SH-SY5 Y cells,according to the method of randomized block is divided into control group(without medication),rotenone(final concentration of 0.1 uM)model,curcumin pretreatment group(final concentration were 0.5 uM and 1.0 uM and 5.0 uM and 10.0 uM),a total of six groups.The cell vitality,determined by MTT testing flow cytometry instrument to detect the contents of ROS,Western blot method to detect intracellular SIRT3,FOXO3 a and MnSOD and CAT protein expression.The results 1.MTT: Determined by MTT: curcumin 0.5 umol/L-1.0 umol/L began to rotenone cause cellular damage,the protective effects of cell vitality than fish cane ketone damage group has significant difference were observed in the increasing significance(P < 0.01),and 1.0 umol/L has the strongest;5.0 umol/L when its protective effect began to decline,a separate role in SH SY5 Y cells to lower its vitality,but and fish cane ketone in SH SY5 Y cells makes its vitality is fish cane ketone damage group increased,still performs the function of protect cells,instead of showing synergy damage,but there was no statistically significant difference(P > 0.05).2.The influence of flow cytometry instrument to detect the contents of intracellular ROS: 1.0 umol/L rotenone processing cells after 24 h,intracellular ROS levels higher than the control group(P < 0.01);0.5 umol/L,1.0 umol/L curcumin treatment group compared with blank control group and fish cane ketone group of intracellular ROS reduced(P < 0.01);5.0 umol/L,10 umol/L curcumin treatment group there was no statistically significant difference compared with rotenone group(p > 0.05)3.Western blot detection SIRT3,FOXO3 a,Mn SOD and CAT protein expression: rotenone express lower treatment group than the control group,0.5 umol/L,1.0 umol/L curcumin treatment group than the control group,rotenone expression increases,the difference was statistically significant(P < 0.01);5.0 umol/L,10.0 umol/L a fish cane ketone group has no statistically significant difference(P > 0.05)Conclusion 1.Rotenone has obvious neurotoxicity,its toxic effects in concentration dependence: appropriate concentration could be used to the preparation of PD model of SH-SY5 Y cells,with high will directly cause cell death.2.The SH SY5 Y cells induced by rotenone cell vitality reduced in PD model,intracellular ROS content increased,Sirt3,FOXO3 a,Mn-reduce the expression of SOD and CAT.3.The curcumin may express,through induction of SIRT3 FOXO3 a to acetylation activation,which in turn increases the expression of MN-SOD and CAT reduce content of ROS in cells,which participate in the PD neural protection.