The Dependence Of ROS Signaling Regulation Via SOD1 Inhibition On The Concentration Of The Inbibitors

Reactive oxygen species(ROS)is a kind of toxic byproducts produced during the metabolism of aerobic organisms,which can cause oxidative damage to normal cells and thus are strictly controlled by cells.Cu/Zn superoxide dismutase(SOD1)is an important antioxidant enzyme in the cell.It catalyzes O2·-disproportionation to H2O2 and O2,.Local high concentration of H2O2 can oxidize PTP,PTEN and other phosphatase's cysteine residues,disording signal pathway.Signaling pathway is the way for transmission of external signals and corresponding,mainly depends on the cascade amplification and phosphorylation of several signal protein,such as extracellular regulated protein kinase(ERK),protein kinase B(AKT),phosphorylated 3-kinase(PI3K)and nuclear factor kappa B(NF-?B).LD100,a SOD1 inhibitor,can decrease the phosphorylation of ERK,PI3K,AKT,I?B and NF-?B,resulting in the inhibition of ERX,P3K and NF-?B signal pathway.Besides,there is a crosstalk between the ERK and the PI3K pathway,which can be inbitted by LD100.The NF-?B pathway is the downstream path of the PI3K pathway.We also explore the effect of LD100 on cell activity.LD100 could inhibit the growth of cancer cell lines,such as HeLa and DU145,arresting the cell cycle in G1 phase,but has little influence on normal cell line,such as RWPE1.And,LD100 can down-regulate the expression of Bcl-2 protein,activate the caspase 3 protein,cleave the PARP protein,and finally result in the fragment of DNA.Besides,LD100 could increase the content of ONOO-in the cells,but this have little connect with the apoptosis induced by LD100.