NOS1AP O-GlcNAc Modification Involved in Neuron Apoptosis Induced by Excitotoxicity

Liang Zhu; Tao Tao; Dongmei Zhang; Xiaojuan Liu; Kaifu Ke; Aiguo Shen

doi:10.3390/ijms160716560

NOS1AP O-GlcNAc Modification Involved in Neuron Apoptosis Induced by Excitotoxicity

Int J Mol Sci. 2015 Jul 21;16(7):16560-75. doi: 10.3390/ijms160716560.

Authors

Liang Zhu^{1

2}, Tao Tao^{3

4}, Dongmei Zhang^{5

6}, Xiaojuan Liu^{7

8}, Kaifu Ke⁹, Aiguo Shen^{10

11

12}

Affiliations

¹ 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.
² The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zhuliang_nt@163.com.
³ 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.
⁴ The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. nttaotao@ntu.edu.cn.
⁵ 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.
⁶ The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. zdm@ntu.edu.cn.
⁷ 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.
⁸ The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. lxj@ntu.edu.cn.
⁹ 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.
¹⁰ 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.
¹¹ The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226000, China. shag@ntu.edu.cn.
¹² Department of Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226000, China. shag@ntu.edu.cn.

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.

Keywords: NOS1AP; O-GlcNAc modification; excitotoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylglucosamine / metabolism*
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Apoptosis*
Glutamic Acid / toxicity
Glycosylation
HEK293 Cells
Humans
Male
Neurons / drug effects
Neurons / metabolism*
Nitric Oxide Synthase Type I / metabolism
PC12 Cells
Protein Processing, Post-Translational*
Rats
Rats, Sprague-Dawley

Substances

Adaptor Proteins, Signal Transducing
NOS1AP protein, rat
Glutamic Acid
Nitric Oxide Synthase Type I
Acetylglucosamine