Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death

Matés, José M.; Pérez‐Gómez, Cristina; Castro, Ignacio Núñez de; Asenjo, Maite; Márquez, Javier

doi:10.1016/s1357-2725(01)00143-1

Cited by 295 publications

(205 citation statements)

References 149 publications

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…Glutamate can be further deaminated to form α-ketoglutarate and thus enter the citric acid cycle for energy metabolism. Glutamate also preserves total GSH levels after oxidative stress (22,30). Our data indicate that p53-inducible GLS2 regulates intracellular glutamine metabolism and ROS levels and promotes antioxidant defense through controlling the GSH/GSSG ratio, although we do not exclude the additional possibility that regeneration of GSH from GSSG is increased by GLS2 expression.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species

Suzuki

Tanaka

Poyurovsky

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

591

492

View full text Add to dashboard Cite

We identified a p53 target gene, phosphate-activated mitochondrial glutaminase (GLS2), a key enzyme in conversion of glutamine to glutamate, and thereby a regulator of glutathione (GSH) synthesis and energy production. GLS2 expression is induced in response to DNA damage or oxidative stress in a p53-dependent manner, and p53 associates with the GLS2 promoter. Elevated GLS2 facilitates glutamine metabolism and lowers intracellular reactive oxygen species (ROS) levels, resulting in an overall decrease in DNA oxidation as determined by measurement of 8-OH-dG content in both normal and stressed cells. Further, siRNA down-regulation of either GLS2 or p53 compromises the GSH-dependent antioxidant system and increases intracellular ROS levels. High ROS levels following GLS2 knockdown also coincide with stimulation of p53-induced cell death. We propose that GLS2 control of intracellular ROS levels and the apoptotic response facilitates the ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress. Indeed, overexpression of GLS2 reduces the growth of tumor cells and colony formation. Further, compared with normal tissue, GLS2 expression is reduced in liver tumors. Thus, our results provide evidence for a unique metabolic role for p53, linking glutamine metabolism, energy, and ROS homeostasis, which may contribute to p53 tumor suppressor function.glutathione antioxidant | glutaminolysis | tumor suppression | apoptosis

show abstract

Section: Discussionmentioning

confidence: 67%

“…Glutamine preserves total GSH levels after oxidative damage, making it a component of the cellular antioxidant defense (22). GLS2 plays a critical role by up-regulating GSH levels upon oxidative stress (23,24).…”

Section: Gls2mentioning

confidence: 99%

Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species

Suzuki

Tanaka

Poyurovsky

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

591

492

View full text Add to dashboard Cite

show abstract

“…In addition, the YP used in this experiment contained a relatively higher (by 4.47%) content of glutamine. As a precursor for biosynthesis of cellular antioxidant glutathione, glutamine has been demonstrated to attenuate oxidative stress and related gene expression in mammals (Mates et al 2002;Tsai et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Inclusion of yeast-derived protein in weanling diet improves growth performance, intestinal health, and anti-oxidative capability of piglets

Hu¹,

Che²,

Su³

et al. 2014

CZECH J ANIM SCI

View full text Add to dashboard Cite

ABSTRACT:The effects of yeast-derived protein (YP) on growth performance, intestinal health, and oxidative status of weanling piglets were investigated. A total of 80 weaned piglets (PIC 327 × 1050, 26 ± 2 days old, 6.20 ± 0.10 kg) were randomly allocated into 2 groups, 5 pens per each group and 8 piglets per each pen, receiving control diet and diet with inclusion of 4% YP at the expenses of fish meal (YP diet) for a period of 28 days. The diets were formulated to contain similar nutrient levels. Compared with control, piglets fed YP diet had markedly higher overall average daily growth (+14%, P < 0.05) and lower final feed conversion ratio (−8%, P < 0.01). Concentrations of serum serine, cystathionine, histidine, hydroxyproline, and urea were decreased in piglets fed YP diet (P < 0.05), whereas alanine and aspartate were increased (P < 0.01). Moreover, serum antioxidant enzyme activity (glutathione peroxidase) was markedly increased (+19%, P < 0.01) in piglets fed YP diet relative to piglets fed control diet. In addition, feeding YP diet considerably (P < 0.05) increased the copy numbers of lactobacilli and total bacteria in the colon of piglets at the end of the experiment. Furthermore, the mRNA abundance of innate immunity-related genes (TLR4, NF-κB1, and IL-6) was increased (P < 0.06) in the ileum of piglets fed YP diet. Collectively, results of this study indicated that diet with the inclusion of YP improved growth performance and partially enhanced anti-oxidative capability as well as intestinal innate immunity of weaning piglets.

show abstract

“…Gln also prevents caspase-8 activation in human intestinal epithelial T84 cells cultured with the proapoptotic Clostridium difficile toxin A (21). Another potential mechanisms of Gln action is the pathway of glutathione, an antioxidant compound that detoxifies reactive oxygen species and has potent antiapoptotic effects (22,23). However, although the glutathione pathway is widely implicated in the antiapoptotic action of Gln on immune cells, Evans et al (19) have demonstrated that this was not the case in the intestinal HT-29 cell line.…”

Section: Discussionmentioning

confidence: 99%

Glutamine Regulates the Human Epithelial Intestinal HCT-8 Cell Proteome under Apoptotic Conditions

Deniel

Marion‐Letellier

Charlionet

et al. 2007

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Glutamine plays a key role in the metabolism of rapidly dividing cells, including enterocytes and lymphocytes, which may contribute to its beneficial clinical effects. Gut mucosal homeostasis is achieved through a balance between cell proliferation and apoptosis. In T cells, glutamine up-regulates antiapoptotic proteins and down-regulates proapoptotic proteins. In gut mucosa, glutamine prevents apoptosis in rat epithelial cell lines, whereas glutamine starvation induces apoptosis through caspase activation. Finally glutamine specifically prevents tumor necrosis factor-␣-related apoptosis in the human intestinal cell line HT-29. Comparative functional proteomics enables the characterization of each differentially expressed protein in intestinal cells in response to modifications of nutritional environment. The influence of glutamine on intestinal proteome expression in apoptotic conditions has not been studied and evaluated. This comparative proteomics study was performed in the human epithelial intestinal cell line HCT-8 under experimental apoptotic conditions to investigate the influence of glutamine on protein expression during apoptosis. The pharmaconutritional effects of glutamine were determined under 2 mM (physiological concentration) and 10 mM (pharmaconutritional concentration) conditions. About 1,800 protein spots were revealed in both conditions. Comparative assessments indicated that 28 proteins were differentially expressed significantly (i.e. at least 2-fold modulated and Student's t test with p < 0.05) in response to an increase of glutamine concentration in the culture medium. Twenty-four proteins were identified by mass spectrometry and associated databases. From these proteins, 34% are involved in cell cycle and apoptosis mechanisms, 17% are involved in signal transduction, and 13% are involved in cytoskeleton organization. These data were integrated in a proposed schema of the interactome under apoptotic conditions. In conclusion, this study provides the first holistic picture of proteome mod-

show abstract

Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death

Cited by 295 publications

References 149 publications

Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species

Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species

Inclusion of yeast-derived protein in weanling diet improves growth performance, intestinal health, and anti-oxidative capability of piglets

Glutamine Regulates the Human Epithelial Intestinal HCT-8 Cell Proteome under Apoptotic Conditions

Contact Info

Product

Resources

About