Phycocyanin Promotes Somatic Reprogramming By Regulating Oxidative Stress And Cellular Metabolism

Reactive oxygen species plays an important role in normal cells physiological regulation.However,the accumulation of a large amount of reactive oxygen species in cells can lead to oxidative stress.During somatic cells reprogramming,oxidative stress can cause a series of damage to cells,for instance,blocks the reprogramming,and thus restrict the extensive application of iPS technology.In this study,phycocyanin,a natural antioxidant,was used to investigate its impact on somatic cells reprogramming efficiency and further research the mechanism of phycocyanin affecting reprogramming.The results showed that phycocyanin at a concentration of 160 ?g/ml was added to DOX-induced reprogramming medium and treated for 12 days to increasereprogramming efficiency by 2-3 folds.Further analysis showed that phycocyanin treatment significantly up-regulated the pluripotency genes expression level,accelerated MET and promoted cell cycle progression,thereby accelerating the reprogramming process.In addition,phycocyanin up-regulated the expression levels of Nrf2 and Hif1? genes,activated downstream antioxidant genes Cat and Gpx2,and reduced the level of reactive oxygen species.At the same time,phycocyanin inhibits the activation of mTOR,upregulated AMPK and FOXO3,promoted autophagy,and rescued the block of autophagy induced by 3-MA.Phycocyanin accelerated mitochondrial remodeling during reprogramming,promoted glucose uptake in cells,increased the production of pyruvic acid and lactic acid,metabolites of glycolysis,and promoted the conversion of cellular metabolism from oxidative phosphorylation to glycolysis.The results of this study laid the foundation for deep understanding of the role of proteins with antioxidant activity in somatic cells reprogramming,and laid the technical foundation for the establishment of more efficient iPS cell induction technology.