Glutamine enhances heat shock protein 70 expression via increased hexosamine biosynthetic pathway activity

Hamiel, Christine; Pinto, Shanti M.; Hau, Ann; Wischmeyer, Paul E.

doi:10.1152/ajpcell.00240.2009

Cited by 97 publications

(92 citation statements)

References 30 publications

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“…1), it has been postulated that glutamine may work in an O-GlcNAc-dependent manner. In support of this hypothesis, in vivo treatment with glutamine has been shown to elevate OGlcNAc levels (Singleton and Wischmeyer 2008;Hamiel et al 2009). Moreover, the ability of glutamine to induce HSP70 is attenuated in cells in which O-GlcNAc levels have been lowered (Hamiel et al 2009).…”

Section: Heat Shock Protein Expressionmentioning

confidence: 92%

“…In support of this hypothesis, in vivo treatment with glutamine has been shown to elevate OGlcNAc levels (Singleton and Wischmeyer 2008;Hamiel et al 2009). Moreover, the ability of glutamine to induce HSP70 is attenuated in cells in which O-GlcNAc levels have been lowered (Hamiel et al 2009). In heat-stressed cells and a septic mouse model, glutamine treatment appears to promote the nuclear accumulation of HSF-1 and Sp1 in an OGlcNAc-dependent manner (Singleton and Wischmeyer 2008;Hamiel et al 2009).…”

Section: Heat Shock Protein Expressionmentioning

confidence: 92%

“…Moreover, the ability of glutamine to induce HSP70 is attenuated in cells in which O-GlcNAc levels have been lowered (Hamiel et al 2009). In heat-stressed cells and a septic mouse model, glutamine treatment appears to promote the nuclear accumulation of HSF-1 and Sp1 in an OGlcNAc-dependent manner (Singleton and Wischmeyer 2008;Hamiel et al 2009). Although the mechanisms underlying the above observations remain unclear, it may be explained in part by the observations of Lim and Chang who demonstrated that increased levels of O-GlcNAc are associated with a more soluble pool of Sp1 during thermal stress (Lim and Chang 2006).…”

Section: Heat Shock Protein Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Groves

Lee

Yildirir

et al. 2013

Cell Stress and Chaperones

116

112

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O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) is a ubiquitous and dynamic post-translational modification known to modify over 3,000 nuclear, cytoplasmic, and mitochondrial eukaryotic proteins. Addition of O-GlcNAc to proteins is catalyzed by the O-GlcNAc transferase and is removed by a neutral-N-acetyl-β-glucosaminidase (OGlcNAcase). O-GlcNAc is thought to regulate proteins in a manner analogous to protein phosphorylation, and the cycling of this carbohydrate modification regulates many cellular functions such as the cellular stress response. Diverse forms of cellular stress and tissue injury result in enhanced O-GlcNAc modification, or O-GlcNAcylation, of numerous intracellular proteins. Stress-induced OGlcNAcylation appears to promote cell/tissue survival by regulating a multitude of biological processes including: the phosphoinositide 3-kinase/Akt pathway, heat shock protein expression, calcium homeostasis, levels of reactive oxygen species, ER stress, protein stability, mitochondrial dynamics, and inflammation. Here, we will discuss the regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage. We will also discuss the misregulation of O-GlcNAc in diseases commonly associated with the stress response, namely Alzheimer's and Parkinson's diseases. Finally, we will highlight recent advancements in the tools and technologies used to study the O-GlcNAc modification.

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Section: Heat Shock Protein Expressionmentioning

confidence: 92%

Section: Heat Shock Protein Expressionmentioning

confidence: 92%

Section: Heat Shock Protein Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Groves

Lee

Yildirir

et al. 2013

Cell Stress and Chaperones

116

112

View full text Add to dashboard Cite

show abstract

“…20,21 The ability of cells to respond to and survive stressful conditions is known to be influenced by glucose and glutamine-dependent O-GlcNAcylation through the hexosamine biosynthetic pathway (HBP), in which both mentioned substrates are enzymatically converted to the high-energy metabolite UDP-N-acetylglucosamine (UDP-GlcNAc), which is then covalently attached to serine, threonine, or tyrosine residues of proteins under UDP release. [22][23][24][25] In contrast to other types of O-and N-linked glycosylation, O-GlcNAcylation is a primarily nuclear and cytosolic glycosylation with a single O-GlcNAc moiety and in contrast to more complex glycan structures, a dynamic process more akin to phosphorylation. 20 The enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) keep the rates of glycosylation and deglycosylation in a dynamic equilibrium and ready to respond to environmental stimuli, such as the availability of glucose, combined with a hyperosmolar injurious stress.…”

mentioning

confidence: 99%

Dynamic O-Linked N-Acetylglucosamine Modification of Proteins Affects Stress Responses and Survival of Mesothelial Cells Exposed to Peritoneal Dialysis Fluids

Bender

Vychytil

Bialas

et al. 2014

Journal of the American Society of Nephrology

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The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-Dglucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD.

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“…21 Hamiel et al 22 found that Gln metabolism enhances HSP70 expression by increasing the hexosamine biosynthetic pathway activity, with the O-glycosylation, nuclear translocation, and transcriptional activation of Sp1 and heat shock factor-1 (HSF1) being responsible. Zachara et al 23 reported that stress (including thermal stress) applied to cells rapidly increases the O-glycosylation of intracellular proteins, which is associated with increased HSP70 expression.…”

Section: Discussionmentioning

confidence: 99%

Combined microwave irradiation and intraarticular glutamine administration‐induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model

Fujita

Nakagawa

Takahashi

et al. 2011

Journal Orthopaedic Research

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The objective of the present study was to investigate the effects of heat stimulation and glutamine (Gln) on the expression of extracellular matrix genes and heat shock protein 70 (HSP70) in rat articular cartilage in vivo and to determine whether HSP70 expression achieved with a combination of microwave (MW) and Gln suppresses osteoarthritis (OA) progression in a rat OA model. Stimulation at 40 W was assumed to be appropriate in the present study, and the effects of heat treatment at this intensity were evaluated. Articular cartilage was collected at 8 h after heat stimulation and/or intraarticular Gln administration, and total RNA was extracted. The expression of HSP70, aggrecan, and type II collagen was quantified using real-time RT-PCR. Cartilage samples from the OA model were subjected to hematoxylin and eosin (HE) and safranin O staining. HSP70 and aggrecan expression was greatest in a group receiving both MW and Gln. In the rat OA model, the severity of OA was significantly milder in a group receiving MW and Gln than in the control group. HSP70, stimulated by the combination of MW heat and Gln, may be involved in the suppression of OA progression. ß

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Glutamine enhances heat shock protein 70 expression via increased hexosamine biosynthetic pathway activity

Cited by 97 publications

References 30 publications

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Dynamic O-Linked N-Acetylglucosamine Modification of Proteins Affects Stress Responses and Survival of Mesothelial Cells Exposed to Peritoneal Dialysis Fluids

Combined microwave irradiation and intraarticular glutamine administration‐induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model

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