Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018, 162(3):243-248 | DOI: 10.5507/bp.2018.042

The effects of O-GlcNAc alteration on Alzheimer-like neurodegeneration in SK-N-SH cells

Nan Dinga, Peng Penga, Yu-jing Chua, Jing-jing Wanga, Shu-yi Chena, Renuka Arulthasa, Yan-qiu Denga
a Department of Pathophysiology, Basic Medical College, Tianjin Medical University, 300070, China

Background: O-GlcNAcylation is a highly dynamic post-translational modification that plays a key role in regulating phosphorylation of protein and cell survival. The proteins O-GlcNAcylation level is regulated dynamically by O-GlcNAc transferase (OGT) and β-N-acetylglucosaminidase (O-GlcNAcase, OGA). Although previous studies have suggested the role of O-GlcNAcylation in neurodegenerative diseases, the mechanism of O-GlcNAcylation in Alzheimer's disease (AD) remains unclear.

Methods: The decrease of O-GlcNAcylation by alloxan, an OGT inhibitor, and increase by NAG-thiazolines (NAG-Ae), an O-GlcNAcase inhibitor were tested to investigate the effects of O-GlcNAc alteration on AD like neurodegeneration in SK-N-SH cells.

Results: The level of O-GlcNAcylation was decreased in alloxan treated cells and increased in NAG-Ae treated cells. Meanwhile, it was observed that both abnormal phosphorylation of NFs in cell bodies and apoptosis induced by alloxan treatment can be resisted by pretreatment or simultaneous treatment with appropriate NAG-Ae.

Conclusion: These results demonstrated that increasing O-GlcNAc with NAG-Ae protected AD like neurodegeneration from NFs hyperphosphorylation and the cell loss, suggesting the role of O-GlcNAc in the pathogenesis and therapy of AD.

Keywords: O-GlcNAcylation; O-GlcNAcase; O-GlcNAc transferase; neurofilament phosphorylation; Alzheimer's disease

Received: September 18, 2017; Accepted: July 17, 2018; Prepublished online: August 28, 2018; Published: September 18, 2018  Show citation

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Ding, N., Peng, P., Chu, Y., Wang, J., Chen, S., Arulthas, R., & Deng, Y. (2018). The effects of O-GlcNAc alteration on Alzheimer-like neurodegeneration in SK-N-SH cells. Biomedical papers, 162(3), 243-248. doi: 10.5507/bp.2018.042
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