scholarly journals Fueling the fire: emerging role of the hexosamine biosynthetic pathway in cancer

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Neha M. Akella ◽  
Lorela Ciraku ◽  
Mauricio J. Reginato
Keyword(s):  
Biosynthetic Pathway ◽  
Hexosamine Biosynthetic Pathway

scholarly journals 256 The metabolic effects of glutamine in the heart beyond anaplerosis: role of the hexosamine biosynthetic pathway

2011 ◽  
Vol 3 (1) ◽  
pp. 84
Author(s):  
Benjamin Lauzier ◽  
Bertrand Bouchard ◽  
Fanny Vaillant ◽  
Francois Labarthe ◽  
Caroline Daneault ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Metabolic Effects ◽  
Hexosamine Biosynthetic Pathway

Decreased insulin-stimulated GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats

1999 ◽  
Vol 276 (5) ◽  
pp. E907-E912 ◽  
Author(s):  
Kentaro Kawanaka ◽  
Dong-Ho Han ◽  
Lorraine A. Nolte ◽  
Polly A. Hansen ◽  
Akira Nakatani ◽  
...  
Keyword(s):  
Cell Surface ◽  
Glucose Transport ◽  
Biosynthetic Pathway ◽  
Glycogen Content ◽  
Hexosamine Biosynthetic Pathway ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Insulin Responsiveness ◽  
Exercise Induced

It was recently found that the effect of an exercise-induced increase in muscle GLUT-4 on insulin-stimulated glucose transport is masked by a decreased responsiveness to insulin in glycogen-supercompensated muscle. We evaluated the role of hexosamines in this decrease in insulin responsiveness and found that UDP- N-acetyl hexosamine concentrations were not higher in glycogen-supercompensated muscles than in control muscles with a low glycogen content. We determined whether the smaller increase in glucose transport is due to translocation of fewer GLUT-4 to the cell surface with the 2- N-4-(1-azi-2,2,2-trifluroethyl)-benzoyl-1,3-bis(d-mannose-4-yloxy)-2-propylamine (ATB-[2-3H]BMPA) photolabeling technique. The insulin-induced increase in GLUT-4 at the cell surface was no greater in glycogen-supercompensated exercised muscle than in muscles of sedentary controls and only 50% as great as in exercised muscles with a low glycogen content. We conclude that the decreased insulin responsiveness of glucose transport in glycogen-supercompensated muscle is not due to increased accumulation of hexosamine biosynthetic pathway end products and that the smaller increase in glucose transport is mediated by translocation of fewer GLUT-4 to the cell surface.

Abstract 261: Robust Cardioprotection Afforded by a Previously Unrecognized Link between the Unfolded Protein Response and the Hexosamine Biosynthetic Pathway

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Zhao V Wang ◽  
Yingfeng Deng ◽  
Ningguo Gao ◽  
Zully Pedrozo ◽  
Dan Li ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Biosynthetic Pathway ◽  
Ischemia Reperfusion ◽  
Uridine Diphosphate ◽  
Hexosamine Biosynthetic Pathway ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Rate Limiting

Background: The hexosamine biosynthetic pathway (HBP) generates UDP-GlcNAc (uridine diphosphate N-acetylglucosamine) for glycan synthesis and O-linked GlcNAc (O-GlcNAc) protein modifications. Despite the established role of the HBP in glucose metabolism and multiple diseases, regulation of the HBP remains largely undefined. Methods & Results: Here, we show that spliced Xbp1 (Xbp1s), the most conserved signal transducer of the unfolded protein response (UPR), is a direct transcriptional activator of the HBP. We demonstrate that the UPR triggers activation of the HBP by means of Xbp1s-dependent transcription of genes coding for key, rate-limiting enzymes. We establish that this previously unrecognized UPR-HBP axis is triggered in a variety of stress conditions known to promote O-GlcNAc modification. We go on to demonstrate that Xbp1s, acutely stimulated by ischemia/reperfusion (I/R) in heart, confers robust cardioprotection against I/R injury. We also show that HBP induction is required for this cardioprotective response. Mechanistically, HBP may mediate the adaptive branch of the UPR by activating autophagy and ER-associated degradation. Conclusion: These studies reveal that Xbp1s couples the UPR to the HBP, promoting robust cardioprotection during I/R.

scholarly journals Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2348 ◽  
Author(s):  
Muhammad Tariq Saeed ◽  
Jamil Ahmad ◽  
Shahzina Kanwal ◽  
Andreana N. Holowatyj ◽  
Iftikhar A. Sheikh ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Biosynthetic Pathway ◽  
Genetic Alterations ◽  
Glycolytic Flux ◽  
Model Parameters ◽  
Modeling Framework ◽  
Hexosamine Biosynthetic Pathway ◽  
Degradation Rates ◽  
Acetylglucosamine Transferase

The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.

scholarly journals O-Linked β-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy

2018 ◽  
Vol 132 (2) ◽  
pp. 185-198 ◽  
Author(s):  
Zafer Gurel ◽  
Nader Sheibani
Keyword(s):  
Diabetic Retinopathy ◽  
High Glucose ◽  
Biosynthetic Pathway ◽  
Amino Acid Residues ◽  
Therapeutic Approaches ◽  
Hexosamine Biosynthetic Pathway ◽  
Retinal Pericytes ◽  
A Cell ◽  
Insight Into

The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels. We propose alterations in O-GlcNAc modification of target proteins during diabetes contribute to the development and progression of DR. The O-GlcNAc modification is regulated through hexosamine biosynthetic pathway. We showed this pathway is differentially activated in various retinal vascular cells under high glucose conditions perhaps due to their selective metabolic activity. O-GlcNAc modification can alter protein stability, activity, interactions, and localization. By targeting the same amino acid residues (serine and threonine) as phosphorylation, O-GlcNAc modification can either compete or cooperate with phosphorylation. Here we will summarize the effects of hyperglycemia-induced O-GlcNAc modification on the retinal neurovasculature in a cell-specific manner, providing new insight into the role of O-GlcNAc modification in early loss of retinal pericytes and the pathogenesis of DR.

scholarly journals Impact of Environmental Factors on Stilbene Biosynthesis

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 90
Author(s):  
Alessio Valletta ◽  
Lorenzo Maria Iozia ◽  
Francesca Leonelli
Keyword(s):  
Environmental Factors ◽  
Biosynthetic Pathway ◽  
In Planta ◽  
Organ Cultures ◽  
Related Plant ◽  
Valuable Compounds ◽  
Stilbene Compounds ◽  
Stilbene Biosynthesis ◽  
Abiotic Environmental Factors

Stilbenes are a small family of polyphenolic secondary metabolites that can be found in several distantly related plant species. These compounds act as phytoalexins, playing a crucial role in plant defense against phytopathogens, as well as being involved in the adaptation of plants to abiotic environmental factors. Among stilbenes, trans-resveratrol is certainly the most popular and extensively studied for its health properties. In recent years, an increasing number of stilbene compounds were subjected to investigations concerning their bioactivity. This review presents the most updated knowledge of the stilbene biosynthetic pathway, also focusing on the role of several environmental factors in eliciting stilbenes biosynthesis. The effects of ultraviolet radiation, visible light, ultrasonication, mechanical stress, salt stress, drought, temperature, ozone, and biotic stress are reviewed in the context of enhancing stilbene biosynthesis, both in planta and in plant cell and organ cultures. This knowledge may shed some light on stilbene biological roles and represents a useful tool to increase the accumulation of these valuable compounds.

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