Effect And Mechanism Of Wnt2 Overexpression In PINK1^B9 Transgenic Flies

Objective:To explore the effect of Wnt2 overexpression on PINK1 Mutant Drosophila and its mechanism.Methods:The GAL4-UAS system was used to construct the normal control flies,PINK1^B9 transgenic Drosophila model flies?Parkinson's disease model of Drosophila melanogaster?,the Wnt2overexpression flies and the Wnt2 RNAi flies?each group had more than 100samples?.On the 5th day,the abnormal wings phenotype rate and flying rate of flies were observed.muscle fibres was observed by HE.The morphology of mitochondria was observed by electron microscopy.The contents of Ndufs3?MnSOD??-catenin and Tubulin proteins were detected by Western blot.The mRNA expression levels of ND1,ND42,ND75,sdhB,cytb,COX-1 and FOXO,PGC-1?,NRF1,TFAM were detected by real-time fluorescence quantitative PCR.Complex I and Complex II function was detected by high-resolution mitochondrial respiratory system.The content level of ROS,MDA,GSH and ATP were detected by kit.Results:Wnt2 overexpression protected the PINK1mutant flies.Wnt2 overexpression suppresses muscle degeneration and mitochondrial defects of PINK1 mutant flies.It rescues the functions of Complex I and Complex II?P<0.05?.Ndufs3 protein and MnSOD protein were increased?P<0.05?.Overexpression of Wnt2 Increased mitochondrial OXPHOS complex genes and mitochondrial metabolic synthesis related genes?P<0.05?.It upregulation of ROS,MDA levels in PINK1^B9 transgenic Drosophila model flies?P<0.05?.?-catenin protein levels were no change?P>0.05?.Overexpression of Wnt2 Increased PGC-1?,NRF1,TFAM,FOXO genes in PINK1^B9 transgenic Drosophila model flies?P<0.05?.Conclusions:Overexpression of Wnt2 protects PINK1^B9 transgenic Drosophila models,which is related to the activation of PGC-1?/FOXO/MnSOD signaling pathway to improve mitochondrial function and reduce oxidative stress damage without Wnt/?-catenin signaling pathway.