title: 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.
abstract: Our previous studies have demonstrated that preconditioning with hydrogen peroxide (H(2)O(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(2)O(2) after preconditioning. Here we sought to identify the downstream targets of the JAK-STAT axis that mediated H(2)O(2) preconditioning and the expression of iNOS and COX-2 in the early phase of H(2)O(2) preconditioning. It was shown that (1) Preconditioning with H(2)O(2) at 100 μmol/L for 90 min in PC12 cells induced significant expression of iNOS and COX-2. (2) Pretreatment with the iNOS inhibitor AG (10 μmol/L) or the COX-2 inhibitor NS-398 (10 μmol/L) respectively 20min before H(2)O(2) preconditioning not only inhibits the increased expression of iNOS or COX-2 but also abrogates the protective effects of H(2)O(2) preconditioning against apoptosis induced by oxidative stress. (3) Pretreatment with the JAK inhibitor AG-490 (10 μmol/L) 20 min before H(2)O(2) preconditioning obviously inhibits the up-regulation of iNOS or COX-2 induced by H(2)O(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(2)O(2) preconditioning.
authors.affiliation: Department of Pathogenic Biology & Immunology, Medical College, Shenzhen University, China. yuhm668@yahoo.com.cn
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongzu
authors.initials: H
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Yuanlan
authors.initials: Y
authors.lastname: Shu
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D019610:Cytoprotection; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D053612:Janus Kinases / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D050791:STAT Transcription Factors; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053612:Janus Kinases