ArticleCell death & disease2016
Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Impact of O-GlcNAcylation Elevation on Mitophagy and Glia in the Dentate Gyrus.Journal of neurochemistry · 2025Article
- O-GlcNAcase regulates pluripotency states of human embryonic stem cells.Stem cell reports · 2024Article
- Article
- Targeting ProteinCells · 2022Review
- SREBP1-Induced Glutamine Synthetase Triggers a Feedforward Loop to Upregulate SREBP1 through Sp1 O-GlcNAcylation and Augments Lipid Droplet Formation in Cancer Cells.International journal of molecular sciences · 2021Article
- O-GlcNAcylation: the "stress and nutrition receptor" in cell stress response.Cell stress & chaperones · 2021Review
- O-GlcNAcylation regulates the methionine cycle to promote pluripotency of stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells.Cell death & disease · 2019Article
- O-GlcNAcylation in immunity and inflammation: An intricate system (Review).International journal of molecular medicine · 2019Review
- Role of HIF1International journal of stem cells · 2019Article
- Update on glycerol-3-phosphate acyltransferases: the roles in the development of insulin resistance.Nutrition & diabetes · 2018Review
- The hypoxic tumour microenvironment.Oncogenesis · 2018Review
- ProteinFrontiers in endocrinology · 2018Review
- Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by Suppressing Autophagy via the LPA3/AKT/mTOR Pathway.Frontiers in physiology · 2018Article
- Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell viability without differentiation via LPA receptor mediating manner.Apoptosis : an international journal on programmed cell death · 2017Article
- Impact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathy.Scientific reports · 2017Article
- O-GlcNAc regulation of autophagy and α-synuclein homeostasis; implications for Parkinson's disease.Molecular brain · 2017Article
- O-GlcNAcylation and cardiovascular disease.Biochemical Society transactions · 2017Review
- Stress-induced O-GlcNAcylation: an adaptive process of injured cells.Biochemical Society transactions · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen signaling is critical for stem cell regulation, and oxidative stress-induced stem cell apoptosis decreases the efficiency of stem cell therapy. Hypoxia activates O-linked β-N-acetyl glucosaminylation (O-GlcNAcylation) of stem cells, which contributes to regulation of cellular metabolism, as well as cell fate. Our study investigated the role of O-GlcNAcylation via glucosamine in the protection of hypoxia-induced apoptosis of mouse embryonic stem cells (mESCs). Hypoxia increased mESCs apoptosis in a time-dependent manner. Moreover, hypoxia also slightly increased the O-GlcNAc level. Glucosamine treatment further enhanced the O-GlcNAc level and prevented hypoxia-induced mESC apoptosis, which was suppressed by O-GlcNAc transferase inhibitors. In addition, hypoxia regulated several lipid metabolic enzymes, whereas glucosamine increased expression of glycerol-3-phosphate acyltransferase-1 (GPAT1), a lipid metabolic enzyme producing lysophosphatidic acid (LPA). In addition, glucosamine-increased O-GlcNAcylation of Sp1, which subsequently leads to Sp1 nuclear translocation and GPAT1 expression. Silencing of GPAT1 by gpat1 siRNA transfection reduced glucosamine-mediated anti-apoptosis in mESCs and reduced mammalian target of rapamycin (mTOR) phosphorylation. Indeed, LPA prevented mESCs from undergoing hypoxia-induced apoptosis and increased phosphorylation of mTOR and its substrates (S6K1 and 4EBP1). Moreover, mTOR inactivation by rapamycin (mTOR inhibitor) increased pro-apoptotic proteins expressions and mESC apoptosis. Furthermore, transplantation of non-targeting siRNA and glucosamine-treated mESCs increased cell survival and inhibited flap necrosis in mouse skin flap model. Conversely, silencing of GPAT1 expression reversed those glucosamine effects. In conclusion, enhancing O-GlcNAcylation of Sp1 by glucosamine stimulates GPAT1 expression, which leads to inhibition of hypoxia-induced mESC apoptosis via mTOR activation.
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