title: Annexin A1 nuclear translocation induces retinal ganglion cell apoptosis after ischemia-reperfusion injury through the p65/IL-1β pathway.
abstract: The degeneration of retinal ganglion cells (RGCs) has been identified as a major problem in glaucoma. Previous studies have indicated an association between annexin A1 (ANXA1) and neuronal cell apoptosis, and RGCs apoptosis in acute ischemia-reperfusion was attributed to an increased production of IL-1β. We found that the expression and nuclear translocation of ANXA1 were upregulated in models of acute ischemia-reperfusion in RGCs in vivo. ANXA1 was found to have a promoting effect on the expression of IL-1β in primary cultured RGCs, which could be inhibited by treatment with ANXA1 shRNA or the p65 inhibitor BAY 11-7082. ANXA1 interacted with p65, and recruited it into the nucleus. Chromatin immunoprecipitation assay revealed that ANXA1 accumulated at the IL-1β gene promoter. The reduction of p65 nuclear translocation using a membrane-permeable ANXA1 peptide containing a Ser5Ala mutation led to a decrease in the expression of IL-1β, and acute ischemia-reperfusion induced RGCs apoptosis in vivo. These results indicate that in RGCs, ANXA1 increases IL-1β expression by recruiting p65 to the nucleus, which induces cell apoptosis. The obtained results may help the development of a novel treatment strategy against RGCs apoptosis in acute ischemia-reperfusion injury.
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan 430030, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jieling
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan 430030, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: tjyksys@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D017305:Annexin A1; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C573274:annexin A1, mouse
keywords: Annexin A1; Apoptosis; IL-1β; Nuclear translocation; Retinal ganglion cell