Effect Of PGC-1? Acetylation On MPP+ Induced Core Translocation And Oxidative Damage In SH-SH5Y Cells

BackgroundParkinson's diseasee is a common neuron degeneration disease in the elderly. British doctor James Parkinson has carried on the detailed description of this disease firstly in 1817, its clinical manifestations are mainly static tremor,bradykinesia, myotonia and posture gait disorder, at the same time can be associated with depression, sleep disorder and constipation in patients with non motor symptoms.The basic pathological change is the substantia nigra compacta dopaminergic neuron degeneration and the formation of Lewy bodies, which causes the destruction of the substantia nigra striatum pathway and reduce the content of dopamine.Most of the Parkinson's diseasee for sporadic cases, less than 10% of patients have a family history. For its pathogenesis is not very clear at present,recent researches suggest that many factors contribute to the disease, under the action of multiple factors such as environment, genetic, nerve system aging, through mechanisms of oxidative stress, mitochondrial function defect, proteasome dysfunction, and eventually lead to PD pathological changes and pathogenesis.Studies have shown that mitochondrial dysfunction and reactive oxygen species(reactive oxygen species, ROS) play a very important role in the pathogenesis of PD, which makes it more attention in PD.Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha is an important factor in the biosynthesis of mitochondria and oxidative stress, and plays a strong role in transcriptional regulation, controling the process of oxidation and anti-oxidation, activating a variety of transcription factor to enhance the efficiency of the target gene transcription, and being closely associated with biological oxidative stress.The regulation of PGC-1?is influenced by many kinds of ways, one of which is acetylation regulation, and the effect of PGC-1 ? acetylation on nuclear translocation and cell oxidative stress in nerve cells remains unclear.Clear acetylation,Therefore, definiting the regulating effect of PGC-1 ? acetylation may has an important significance in the protection of mitochondrial function and oxidative stress in nerve cells.ObjectiveTo investigate the effect of GCN5 on PGC-1? acetylation. To clear the influence of acetylation on PGC-1 ? nuclear distribution and cell oxidative stress damage in MPP+ induced SH-SY5 Y cell, exploreing the important molecular regulative mechanisms of PGC-1?.MethodsMTT assay was used to investigate the effect of different concentrations of MPP+?SRC- 3(GCN5 agonist) and MB-3(GCN5 inhibitors) on the vitality of SH-SY5 Y cells,and the effect of different concentrations of SRC- 3 and MB- 3 on the vitality of SH-SY5 Y cells induced by MPP+(1000 um/L). RT-PCR analysis was used to detection the expression of GCN5 m RNA, PGC-1 ? m RNA. Western blot analysis was used to detection the expression of GCN5, apgc-1alpha,cytoplasmic and nucleus PGC-1 ? protein. Flow cytometry instrument was used to test the ROS levels of different groups.ResultMTT method detect that the vitality of SH-SY5 Y cell induced by different concentrations of MPP+ is decreased significantly, and have concentration dependence. The vitality of SH-SY5 Y cell treated with MB-3 and SRC-3 have no obvious changes compared with the control group. RT-PCR and western blot shows that the expression of GCN5 and PGC-1 ? is increased in the SH-SY5 Y cell induced by MPP+ compared with the control group( p<0.01), the expression of GCN5 and cytoplasmic PGC-1 ? is reduced in the SH-SY5 Y cell treated with MB-3 compared with the MPP+ group( p<0.05),while the nucleus PGC-1 ? is increased( p<0.05). And the expression of GCN5 and cytoplasmic PGC-1 ? is increased in the SH-SY5 Y cell treated with SRC-3( p<0.05),while the nucleus pgc-1alpha is reduced( p<0.01). Cellular ROS tests shows that the cellular ROS levels is increased significantly treated with MPP+ compared with the control group(p<0.01). The ROS levels is increased in MPP+ induced SH-SY5 Y cells treated with MB-3 compared with the MPP+ group(p<0.01). On the contrary, the ROS levels is decreased in MPP+ induced SH-SY5 Y cells treated with SRC-3 compared with the MPP+ group(p<0.01).Conclutions1. In the PD model of the MPP+ induced SH-SY5 Y cells, MB- 3 and SRC- 3 can decrease and increase the activity of GCN-5 respectively, they may see as inhibitor and agonist of GCN5 respectively.2. To activate GCN5 can inhibit pgc-1 alpha transfering to the cell nuclear,reducing the pgc-1 alpha activity, increasing cellular oxidative stress damage. To inhibit GCN5 can promote the pgc-1 alpha transfering to the cell nuclear, improving the activity of pgc-1 alpha, restraining the generation of ROS, and playing a role of protecting the nerve cells.