Glutamine protects against apoptosis via downregulation of Sp3 in intestinal epithelial cells

Ban, Kechen; Kozar, Rosemary A.

doi:10.1152/ajpgi.00334.2010

Cited by 27 publications

(13 citation statements)

References 65 publications

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“…Glutamine was added to cells at a concentration of 10 mM, as we have determined this to provide maximal protection. (10)…”

Section: Methodsmentioning

confidence: 99%

Syndecan 1 Plays a Novel Role in Enteral Glutamine’s Gut-Protective Effects of the Postischemic Gut

Peng

Ban²,

Sen³

et al. 2012

Shock

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Syndecan-1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells, and like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan-1 would abrogate the gut protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia/reperfusion (I/R) was utilized. In vitro, intestinal epithelial cells underwent hypoxia/reoxygenation (H/R) to mimic gut I/R with 2mM (physiologic) or 10 mM glutamine supplementation. Permeability, caspase activity, cell growth, and cell surface and shed syndecan-1 were assessed. In vivo, wild type (WT) and syndecan-1 knockout (KO) mice received ± enteral glutamine followed by gut I/R. Intestinal injury was assessed by fluorescent dye clearance and histopathology, permeability as mucosal to serosal clearance ex vivo in everted sacs, and inflammation by myeloperoxidase (MPO) activity. In an in vitro model of gut I/R, glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed syndecan-1 was reduced by glutamine without an increase in syndecan-1 mRNA. In vivo, intestinal permeability, inflammation, and injury were increased after gut I/R in WT mice and further increased in syndecan-1 KO mice. Glutamine’s attenuation of I/R-induced intestinal hyperpermeability, inflammation, and injury were abolished in syndecan-1 KO mice. These results suggest that syndecan-1 plays a novel role in the protective effects of enteral glutamine in the post ischemic gut.

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“…Glutamine was added to cells at a concentration of 10 mM, as we have determined this to provide maximal protection. (10)…”

Section: Methodsmentioning

confidence: 99%

Syndecan 1 Plays a Novel Role in Enteral Glutamine’s Gut-Protective Effects of the Postischemic Gut

Peng

Ban²,

Sen³

et al. 2012

Shock

Self Cite

View full text Add to dashboard Cite

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“…SP family members SP1/3/4 have been implicated as non-oncogenic addiction events in pancreatic cancer xenograft experiments23. Yet, reduced SP3 expression is associated with decreased apoptosis-related caspase activity24 and decreased oncogenicity252627 whereas elevated levels in LS174 modified colon carcinoma cells leads to increased apoptosis and prevents tumor formation in nude mice28.…”

Section: Discussionmentioning

confidence: 99%

A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors

Katigbak

Cencic

Robert

et al. 2016

Sci Rep

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An enormous amount of tumor sequencing data has been generated through large scale sequencing efforts. The functional consequences of the majority of mutations identified by such projects remain an open, unexplored question. This problem is particularly complicated in the case of rare mutations where frequency of occurrence alone or prediction of functional consequences are insufficient to distinguish driver from passenger or bystander mutations. We combine genome editing technology with a powerful mouse cancer model to uncover previously unsuspected rare oncogenic mutations in Burkitt’s lymphoma. We identify two candidate tumor suppressors whose loss cooperate with MYC over-expression to accelerate lymphomagenesis. Our results highlight the utility of in vivo CRISPR/Cas9 screens combined with powerful mouse models to identify and validate rare oncogenic modifier events from tumor mutational data.

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“…Because glutamine is necessary for normal cell growth, we considered the physiological concentration found in the media as our control group. Glutamine was added to cells up to 20 mM, as previously described (3).…”

Section: Methodsmentioning

confidence: 99%

Glutamine activates peroxisome proliferator-activated receptor-γ in intestinal epithelial cells via 15-S-HETE and 13-OXO-ODE: a novel mechanism

Ban

Sprunt

Martin

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Glutamine possesses gut-protective effects both clinically and in the laboratory. We have shown in a rodent model of mesenteric ischemia-reperfusion that enteral glutamine increased peroxisome proliferator-activated receptor-γ (PPAR-γ) and was associated with a reduction in mucosal injury and inflammation. The mechanism by which glutamine activates PPAR-γ is unknown, and we hypothesized that it was via a ligand-dependent mechanism. Intestinal epithelial cells, IEC-6, were co-transfected with PPAR-γ response element-luciferase promoter/reporter construct. Cells were pretreated with increasing concentrations of glutamine ± GW9662 (a specific antagonist of PPAR-γ) and analyzed for PPAR-γ response element luciferase activity as an indicator of PPAR-γ activation. PPAR-γ nuclear activity was assessed by electrophoretic mobility shift assay. Cell lysates were subjected to tandem mass spectroscopy for measurement of prostaglandin and lipoxygenase metabolites. A time- and concentration-dependent increase in PPAR-γ transcriptional activity, but not mRNA or protein, was demonstrated. Activity was abrogated by the PPAR-γ inhibitor, GW9662, and changes in activity correlated with PPAR-γ nuclear binding. Glutamine, via degradation to glutamate, activated the metabolic by-products of the lipoxygenase and linoleic acid pathways, 15-S-hydroxyeicosatetraenoic acid and dehydrogenated 13-hydroxyoctaolecadienoic acid, known endogenous PPAR-γ ligands in the small bowel. This novel mechanism may explain the gut-protective effects of enteral glutamine.

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Glutamine protects against apoptosis via downregulation of Sp3 in intestinal epithelial cells

Cited by 27 publications

References 65 publications

Syndecan 1 Plays a Novel Role in Enteral Glutamine’s Gut-Protective Effects of the Postischemic Gut

Syndecan 1 Plays a Novel Role in Enteral Glutamine’s Gut-Protective Effects of the Postischemic Gut

A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors

Glutamine activates peroxisome proliferator-activated receptor-γ in intestinal epithelial cells via 15-S-HETE and 13-OXO-ODE: a novel mechanism

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