title: Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia/Reperfusion-Induced Damage to CA1 Hippocampal Neurons.
abstract: Nitric oxide (NO) can regulate signaling pathways via S-nitrosylation. Fyn can be post-translationally modified in many biological processes. In the present study, using a rat four-vessel-occlusion ischemic model, we aimed to assess whether Fyn could be S-nitrosylated and to evaluate the effects of Fyn S-nitrosylation on brain damage. In vitro, Fyn could be S-nitrosylated by S-nitrosoglutathione (GSNO, an exogenous NO donor), and in vivo, endogenous NO synthesized by NO synthases (NOS) could enhance Fyn S-nitrosylation. Application of GSNO, 7-nitroindazole (7-NI, an inhibitor of neuronal NOS) and hydrogen maleate (MK-801, the N-methyl-d-aspartate receptor (NMDAR) antagonist) could decrease the S-nitrosylation and phosphorylation of Fyn induced by cerebral ischemia/reperfusion (I/R). Cresyl violet staining validated that these compounds exerted neuroprotective effects against the cerebral I/R-induced damage to hippocampal CA1 neurons. Taken together, in this study, we demonstrated that Fyn can be S-nitrosylated both in vitro and in vivo and that inhibiting S-nitrosylation can exert neuroprotective effects against cerebral I/R injury, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stroke and the development of novel treatment strategies.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221002, China. hlyxuzhou@163.com.|Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou 221002, China. hlyxuzhou@163.com.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Hao
authors.affiliation: Research Center for Biochemistry and Molecular Biology, and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221002, China. xuewenwei@126.com.|Department of Laboratory Medicine, Affiliated Municipal Hospital of Xuzhou Medical University, Xuzhou 221002, China. xuewenwei@126.com.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Wei
authors.affiliation: Research Center for Biochemistry and Molecular Biology, and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221002, China. gpxuzhou8912@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Research Center for Biochemistry and Molecular Biology, and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221002, China. hlyxuzhou@163.com.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Research Center for Biochemistry and Molecular Biology, and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221002, China. suhuaqi@xzmc.edu.cn.
authors.forename: Suhua
authors.initials: S
authors.lastname: Qi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D016291:Dizocilpine Maleate; D052248:Nitric Oxide Synthase Type I; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn
keywords: Fyn; S-nitrosylation; cerebral ischemia and reperfusion; neuroprotection; phosphorylation