Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes
Joint Authors
Rahman, Md. Ataur
Hwang, Hongik
Cho, Yoonjeong
Rhim, Hyewhon
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-13
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
American Psychological Association (APA)
Rahman, Md. Ataur& Hwang, Hongik& Cho, Yoonjeong& Rhim, Hyewhon. 2019. Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1204519
Modern Language Association (MLA)
Rahman, Md. Ataur…[et al.]. Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1204519
American Medical Association (AMA)
Rahman, Md. Ataur& Hwang, Hongik& Cho, Yoonjeong& Rhim, Hyewhon. Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1204519
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204519