Role of ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H_2O_2 preconditioning

AIM: To explore the role of extracellular signal-regulated kinases ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H2O2 preconditioning in PC12 cells.METHODS: In PC12 cells,the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress-induced injury was set up.The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258.The percent of apoptotic cells was determined by flow cytometry(FCM) with propidium iodide staining.The levels of p-ERK1/2 and p-STAT3 expression were detected by Western blotting assay.RESULTS: Preconditioning with H2O2 at concentration of 100 μmol/L for 90 min obviously inhibited apoptosis induced by 300 μmol/L H2O2,and both ERK1/2 and STAT3 were activated.UO126(10 μmol/L,an inhibitor of ERK1/2) or AG-490(10μmol/L,an inhibitor of JAK2) significantly blocked the cytoprotection effect of H2O2 preconditioning.Moreover,UO126(10 μmol/L) also markedly inhibited the up-regulation of p-STAT3 expression by H2O2 preconditioning.CONCLUSION: H2O2 preconditioning activates ERK1/2-STAT3 signal pathway,which may be one of the mechanisms underlying H2O2 preconditioning-induced cytoprotection.