title: NOS1AP O-GlcNAc Modification Involved in Neuron Apoptosis Induced by Excitotoxicity.
abstract: O-Linked N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational modification that cycles on and off serine and threonine residues of nucleocytoplasmic and mitochondrial proteins. In addition to cancer and inflammation diseases, O-GlcNAc modification appears to play a critical role during cell apoptosis and stress response, although the precise mechanisms are still not very clear. Here we found that nitric oxide synthase adaptor (NOS1AP), which plays an important part in glutamate-induced neuronal apoptosis, carries the modification of O-GlcNAc. Mass spectrometry analysis identified Ser47, Ser183, Ser204, Ser269, Ser271 as O-GlcNAc sites. Higher O-GlcNAc of NOS1AP was detected during glutamate-induced neuronal apoptosis. Furthermore, with O-GlcNAc sites of NOS1AP mutated, the interaction of NOS1AP and neuronal nitric oxide syntheses (nNOS) decreases. Finally, during glutamate-induced neuronal apoptosis, decreasing the O-GlcNAc modification of NOS1AP results in more severe neuronal apoptosis. All these results suggest that O-GlcNAc modification of NOS1AP exerts protective effects during glutamate-induced neuronal apoptosis.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zhuliang_nt@163.com.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zhuliang_nt@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. nttaotao@ntu.edu.cn.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. nttaotao@ntu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zdm@ntu.edu.cn.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zdm@ntu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. lxj@ntu.edu.cn.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. lxj@ntu.edu.cn.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. kekaifu_nt@126.com.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, the Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. shag@ntu.edu.cn.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. shag@ntu.edu.cn.|Department of Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226000, China. shag@ntu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D018698:Glutamic Acid / Q000633:toxicity; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488082:NOS1AP protein, rat; D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I; D000117:Acetylglucosamine
keywords: NOS1AP; O-GlcNAc modification; excitotoxicity