Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia

Cruzat, Vinícius Fernandes; Bittencourt, Aline Gomes; Scomazzon, Sofia Pizzato; Leite, Jaqueline Santos Moreira; Bittencourt, Paulo Ivo Homem de; Tirapegui, Júlio

doi:10.1016/j.nut.2013.10.019

Cited by 82 publications

(83 citation statements)

References 40 publications

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“…In severe pancreatitis [297] and trauma patients [298], plasma glutamine levels decrease to less than 50 % of its basal levels as compared to control values. Similar effects have also been seen in experimental animal models of sepsis, followed by severe adaptive immune system suppression (low T and B lymphocyte responses) [50,209,299]. In such conditions, plasma glutamine depletion is an independent outcome factor in critically ill patients [300].…”

Section: Physical Exercise Glutamine and Hs Response In Agingmentioning

confidence: 62%

“…Because the organism can synthesize and release glutamine from many tissues, the amino acid is classified as nutritionally non-essential. However, in some catabolic conditions, such as sepsis, recovery from burns or surgery, as well as after high-intensity exercise, glutamine stores (particularly in the skeletal muscle and liver) may fall sharply [208][209][210][211]. This effect is due to increased bodily requirement for glutamine under such conditions, especially by the muscle itself (in the case of high-intensity exercise) and the rapidly dividing cells of the immune system (in the remaining above cases) [50,212].…”

Section: Glutamine Metabolism and Its Importance For The Heat Shock Rmentioning

confidence: 99%

“…Reductions of bodily glutamine concentration may contribute to cell death due to a reduced stress response capacity [209,262]. Interestingly, upon depletion of intracellular glutamine, the uptake of some amino acids, such as leucine, declines and mTORC1 becomes (See figure on previous page.)…”

Section: Glutamine Depletion States Impair the Heat Shock Responsementioning

confidence: 99%

“…The availability of glutamine is thought to be a major factor during critical illnesses, such as sepsis, extensive burns, pancreatitis, trauma, and surgery [209,293,294]. Moreover, the concentration of glutamine in patients diagnosed with T2DM has shown a significant reduction (20 %), when compared with healthy individuals [295].…”

Section: Physical Exercise Glutamine and Hs Response In Agingmentioning

confidence: 99%

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Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Leite

Cruzat

Krause

et al. 2016

Nutrire

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Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid L-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.

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Section: Physical Exercise Glutamine and Hs Response In Agingmentioning

confidence: 62%

Section: Glutamine Metabolism and Its Importance For The Heat Shock Rmentioning

confidence: 99%

Section: Glutamine Depletion States Impair the Heat Shock Responsementioning

confidence: 99%

Section: Physical Exercise Glutamine and Hs Response In Agingmentioning

confidence: 99%

See 2 more Smart Citations

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Leite

Cruzat

Krause

et al. 2016

Nutrire

Self Cite

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“…a major component of the L-glutamine-GSH axis; Cunningham et al 2005, Cruzat et al 2014a, Petry et al 2014. GSH has many protective functions in cellular metabolism, as well as attenuation of oxidative stress and inflammation under catabolic situations (Cruzat & Tirapegui 2009, Cruzat et al 2014b. Furthermore, L-glutamine is a potent modulator of the heat shock protein (HSP) response, possibly through the activation of the glucosamine biosynthetic pathway (HBP) and nutrient sensors such as sirtuin 1 (SIRT1) .…”

Section: Introductionmentioning

confidence: 99%

Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Cruzat¹,

Keane²,

Scheinpflug³

et al. 2014

Journal of Endocrinology

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Obesity-associated diabetes and concomitant inflammation may compromise pancreatic b-cell integrity and function. L-glutamine and L-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. Herein, we studied whether the dipeptide L-alanyl-L-glutamine (Ala-Gln) could exert protective effects via sirtuin 1/HUR (SIRT1/HUR) signalling in b-cells, against detrimental responses following ex vivo stimulation with inflammatory mediators derived from macrophages (IMMs). The macrophages were derived from blood obtained from obese subjects. Macrophages were exposed (or not) to lipopolysaccharide (LPS) to generate a pro-inflammatory cytokine cocktail. The cytokine profile was determined following analysis by flow cytometry. Insulin-secreting BRIN-BD11 b-cells were exposed to IMMs and then cultured with or without Ala-Gln for 24 h. Chronic insulin secretion, the L-glutamineglutathione (GSH) axis, and the level of insulin receptor b (IR-b), heat shock protein 70 (HSP70), SIRT1/HUR, CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome c oxidase IV (COX IV) were evaluated. Concentrations of cytokines, including interleukin 1b (IL1b), IL6, IL10 and tumour necrosis factor alpha (TNFa) in the IMMs, were higher following exposure to LPS. Subsequently, when b-cells were exposed to IMMs, chronic insulin secretion, and IR-b and COX IV levels were decreased, but these effects were partially or fully attenuated by the addition of Ala-Gln. The glutamine-GSH axis and HSP70 levels, which were compromised by IMMs, were also restored by Ala-Gln, possibly due to protection of SIRT1/HUR levels, and a reduction of CHOP expression. Using an ex vivo inflammatory approach, we have demonstrated Ala-Gln-dependent b-cell protection mediated by coordinated effects on the glutamine-GSH axis, and the HSP pathway, maintenance of mitochondrial metabolism and stimulus-secretion coupling essential for insulin release.

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Optimizing glutamine concentration enhances ex vivo expansion of natural killer cells through improved redox status

Ying,

Zhang,

Huang

et al. 2024

Biotechnology Progress

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Amino acids are vital components of the serum‐free medium that influence the expansion and function of NK cells. This study aimed to clarify the relationship between amino acid metabolism and expansion and cytotoxicity of NK cells. Based on analyzing the mino acid metabolism of NK‐92 cells and Design of Experiments (DOE), we optimized the combinations and concentrations of amino acids in NK‐92 cells culture medium. The results demonstrated that NK‐92 cells showed a pronounced demand for glutamine, serine, leucine, and arginine, in which glutamine played a central role. Significantly, at a glutamine concentration of 13 mM, NK‐92 cells expansion reached 161.9 folds, which was significantly higher than 55.5 folds at 2.5 mM. Additionally, under higher glutamine concentrations, NK‐92 cells expressed elevated levels of cytotoxic molecules, the level of cytotoxic molecules expressed by NK‐92 cells was increased and the cytotoxic rate was 68.42%, significantly higher than that of 58.08% under low concentration. In view of the close relationship between glutamine metabolism and intracellular redox state, we investigated the redox status within the cells. This study demonstrated that intracellular ROS levels in higher glutamine concentrations were significantly lower than those under lower concentration cultures with decreased intracellular GSH/GSSG ratio, NADPH/NADP+ ratio, and apoptosis rate. These findings indicate that NK‐92 cells exhibit improved redox status when cultured at higher glutamine concentrations. Overall, our research provides valuable insights into the development of serum‐free culture medium for ex vivo expansion of NK‐92 cells.

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Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia

Abstract: Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.

Cited by 82 publications

References 40 publications

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Optimizing glutamine concentration enhances ex vivo expansion of natural killer cells through improved redox status

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