title: O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity.
abstract: Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. However, directly blocking N-methyl-D-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. Here, we report that nNOS undergoes O-linked-β-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke.
authors.affiliation: Department of Geriatric Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Gong
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Science and Education, Second People's Hospital of Nantong, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Geriatric Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. ntwangjun2016@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, Nantong University, Nantong, 226001, Jiangsu, China. lxj@ntu.edu.cn.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000633:toxicity*; D006031:Glycosylation / Q000187:drug effects; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine
keywords: Excitotoxicity; Neuronal apoptosis; O-GlcNAc glycosylation; nNOS