Glucose Deprivation-induced Increase in Protein O-GlcNAcylation in Cardiomyocytes Is Calcium-dependent

Zou, Luyun; Zhu-Mauldin, Xiaoyuan; Marchase, Richard B.; Paterson, Andrew J.; Liu, Jian; Yang, Qinglin; Chatham, John C.

doi:10.1074/jbc.m112.393207

Cited by 52 publications

(67 citation statements)

References 58 publications

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“…Western blot analysis of protein O-GlcNAcylation in isolated CA1 regions was performed using the CTD 110 O-GlcNAc antibody as previously described (Comer et al, 2001;Zou et al, 2012;Taylor et al, 2014). Briefly, protein concentrations of CA1 homogenates were determined using colorimetric analysis assay (Bio-Rad Laboratories).…”

Section: Methodsmentioning

confidence: 99%

Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus

Stewart¹,

Khan²,

Wang³

et al. 2017

J. Neurosci.

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O-GlcNAcylation is a ubiquitous and dynamic post-translational modification involving the O-linkage of ␤-N-acetylglucosamine to serine/threonine residues of membrane, cytosolic, and nuclear proteins. This modification is similar to phosphorylation and regarded as a key regulator of cell survival and homeostasis. Previous studies have shown that phosphorylation of serine residues on synaptic proteins is a major regulator of synaptic strength and long-term plasticity, suggesting that O-GlcNAcylation of synaptic proteins is likely as important as phosphorylation; however, few studies have investigated its role in synaptic efficacy. We recently demonstrated that acutely increasing O-GlcNAcylation induces a novel form of LTD at CA3-CA1 synapses, O-GlcNAc LTD. Here, using hippocampal slices from young adult male rats and mice, we report that epileptiform activity at CA3-CA1 synapses, generated by GABA A R inhibition, is significantly attenuated when protein O-GlcNAcylation is pharmacologically increased. This dampening effect is lost in slices from GluA2 KO mice, indicating a requirement of GluA2-containing AMPARs, similar to expression of O-GlcNAc LTD. Furthermore, we find that increasing O-GlcNAcylation decreases spontaneous CA3 pyramidal cell activity under basal and hyperexcitable conditions. This dampening effect was also observed on cortical hyperexcitability during in vivo EEG recordings in awake mice where the effects of the proconvulsant pentylenetetrazole are attenuated by acutely increasing O-GlcNAcylation. Collectively, these data demonstrate that the post-translational modification, O-GlcNAcylation, is a novel mechanism by which neuronal and synaptic excitability can be regulated, and suggest the possibility that increasing O-GlcNAcylation could be a novel therapeutic target to treat seizure disorders and epilepsy.

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Section: Methodsmentioning

confidence: 99%

Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus

Stewart¹,

Khan²,

Wang³

et al. 2017

J. Neurosci.

Self Cite

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“…6,7,24,26,29,30) We found an enhancement in cellular O-GlcNAcylation levels when HeLa cells were exposed to arsenite, which indicated that O-GlcNAcylation is involved in the signaling pathways that respond to arsenite exposure.…”

Section: Discussionmentioning

confidence: 85%

“…4,5) OGlcNAcylated proteins also function as regulators of cellular stress responses. O-GlcNAc levels of various subcellular proteins were reported to vary under the conditions such as glucose deprivation, 6) UV-irradiation, heat shock, and oxidative stress. 7) Taken together, O-GlcNAcylation may be involved in stress responses; however, this involvement has not yet been elucidated in detail.…”

mentioning

confidence: 99%

Hyper-<i>O</i>-GlcNAcylation Inhibits the Induction of Heat Shock Protein 70 (Hsp 70) by Sodium Arsenite in HeLa Cells

Miura

Sato

Sakurai

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Lowering extracellular Ca 2+ with EGTA, blocking store-operated Ca 2+ entry with SKF96365 inhibitor, or inhibiting calmodulin-dependent protein kinase II (CaMKII) decreases O-GlcNAcylation. 62 Cytosolic Ca 2+ overload is also known to facilitate ischemia/reperfusion injury, and increased O-GlcNAc levels are shown to be cardioprotective in these models. 63 Recovery associated with increased O-GlcNAc levels correlates with reduction in Ca 2+ -induced stress responses, such as calpain-mediated proteolysis of α-fodrin and CaM-KII.…”

Section: O-glcnacylation Modulates Intracellular Calcium Handlingmentioning

confidence: 99%

The Impact of the Unfolded Protein Response and the Hexosamine Biosynthetic Pathway on Glycosylation

2017

Glycobiology Insights

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Glycan changes, in addition to being traditional mediators of protein quality control, cell signaling, and metabolism, are intimately linked to the progression of cancer and can potentially act as novel therapeutic and diagnostic targets. Despite advances in our understanding that glycosylation plays a key role in protein folding, maturation, and function, there is only limited understanding of the interconnected nature of glycan alterations to endoplasmic reticulum stress, the unfolded protein response, and the development of cancer. This review aims to highlight the interdependence of these pathways and the way they feed into each other to maintain protein quality control, regulate key survival mechanisms, and promote cell viability.

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Glucose Deprivation-induced Increase in Protein O-GlcNAcylation in Cardiomyocytes Is Calcium-dependent

Cited by 52 publications

References 58 publications

Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus

Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus

Hyper-<i>O</i>-GlcNAcylation Inhibits the Induction of Heat Shock Protein 70 (Hsp 70) by Sodium Arsenite in HeLa Cells

The Impact of the Unfolded Protein Response and the Hexosamine Biosynthetic Pathway on Glycosylation

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