JAK-STAT pathway modulates the roles of iNOS and COX-2 in the cytoprotection of early phase of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress

摘要

Our previous studies have demonstrated that preconditioning with hydrogen peroxide (H 2O 2) activated the JAK-STAT pathway that played an important role in the cytoprotection, and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mediated the late phase of cytoprotection induced by high concentration of H 2O 2 after preconditioning. Here we sought to identify the downstream targets of the JAK-STAT axis that mediated H 2O 2 preconditioning and the expression of iNOS and COX-2 in the early phase of H 2O 2 preconditioning. It was shown that (1) Preconditioning with H 2O 2 at 100μmol/L for 90min in PC12 cells induced significant expression of iNOS and COX-2. (2) Pretreatment with the iNOS inhibitor AG (10μmol/L) or the COX-2 inhibitor NS-398 (10μmol/L) respectively 20min before H 2O 2 preconditioning not only inhibits the increased expression of iNOS or COX-2 but also abrogates the protective effects of H 2O 2 preconditioning against apoptosis induced by oxidative stress. (3) Pretreatment with the JAK inhibitor AG-490 (10μmol/L) 20min before H 2O 2 preconditioning obviously inhibits the up-regulation of iNOS or COX-2 induced by H 2O 2 preconditioning. These results suggested that JAK-STAT pathway modulates the roles of iNOS and COX-2 in the cytoprotection of early phase of H 2O 2 preconditioning.