title: Annexin A1 translocates to nucleus and promotes the expression of pro-inflammatory cytokines in a PKC-dependent manner after OGD/R.
abstract: Annexin A1 (ANXA1) is a protein known to have multiple roles in the regulation of inflammatory responses. In this study, we find that after oxygen glucose deprivation/reoxygenation (ODG/R) injury, activated PKC phosphorylated ANXA1 at the serine 27 residue (p27S-ANXA1), and promoted the translocation of p27S-ANXA1 to the nucleus of BV-2 microglial cells. This in turn induced BV-2 microglial cells to produce large amounts of pro-inflammatory cytokines. The phenomenon could be mimicked by either transfecting a mutant form of ANXA1 with its serine 27 residue converted to aspartic acid, S27D, or by using the PKC agonist, phorbol 12-myristate 13-acetate (PMA) in these microglial cells. In contrast, transfecting cells with an ANXA1 S27A mutant (serine 27 converted to alanine) or treating the cells with the PKC antagonist, GF103209X (GF) reversed this effet. Our study demonstrates that ANXA1 can be phosphorylated by PKC and is subsequently translocated to the nucleus of BV-2 microglial cells after OGD/R, resulting in the induction of pro-inflammatory cytokines.
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Baoming
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Clinical laboratory, Center hospital of Wuhan, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, P. R. China.|Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D017305:Annexin A1; D016207:Cytokines; C573274:annexin A1, mouse; D011493:Protein Kinase C; D005947:Glucose