Glutamine Affects Glutathione Recycling Enzymes in a DMBA-Induced Breast Cancer Model

Kaufmann, Yihong; Тодорова, Валентина; Luo, Shaoke; Klimberg, V. Suzanne

doi:10.1080/01635580801956501

Cited by 11 publications

(4 citation statements)

References 43 publications

(51 reference statements)

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“…Thus, in experimental breast cancer, dietary glutamine could paradoxically promote the process of apoptosis. This was reported to be the result of glutathione downregulation [140,141]. These results illustrate the complex regulation exerted by glutamine on transcription factor such as c-myc, i.e.…”

Section: Transcription Factors Involved In the Regulatory Role Of Glusupporting

confidence: 56%

Control of mammalian gene expression by amino acids, especially glutamine

2009

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A growing number of reports clearly demonstrate that amino acids are able to control physiological functions at different levels, including the initiation of protein translation, mRNA stabilization and gene transcription [1][2][3]. Although the molecular mechanisms involved in the control of gene expression by amino Molecular data rapidly accumulating on the regulation of gene expression by amino acids in mammalian cells highlight the large variety of mechanisms that are involved. Transcription factors, such as the basic-leucine zipper factors, activating transcription factors and CCAAT/enhancer-binding protein, as well as specific regulatory sequences, such as amino acid response element and nutrient-sensing response element, have been shown to mediate the inhibitory effect of some amino acids. Moreover, amino acids exert a wide range of effects via the activation of different signalling pathways and various transcription factors, and a number of cis elements distinct from amino acid response element/nutrient-sensing response element sequences were shown to respond to changes in amino acid concentration. Particular attention has been paid to the effects of glutamine, the most abundant amino acid, which at appropriate concentrations enhances a great number of cell functions via the activation of various transcription factors. The glutamine-responsive genes and the transcription factors involved correspond tightly to the specific effects of the amino acid in the inflammatory response, cell proliferation, differentiation and survival, and metabolic functions. Indeed, in addition to the major role played by nuclear factor-jB in the anti-inflammatory action of glutamine, the stimulatory role of activating protein-1 and the inhibitory role of C/EBP homology binding protein in growth-promotion, and the role of c-myc in cell survival, many other transcription factors are also involved in the action of glutamine to regulate apoptosis and intermediary metabolism in different cell types and tissues. The signalling pathways leading to the activation of transcription factors suggest that several kinases are involved, particularly mitogen-activated protein kinases. In most cases, however, the precise pathways from the entrance of the amino acid into the cell to the activation of gene transcription remain elusive.

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Section: Transcription Factors Involved In the Regulatory Role Of Glusupporting

confidence: 56%

Control of mammalian gene expression by amino acids, especially glutamine

2009

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“…The paradoxical effect of Gln on GSH metabolism in tumor and host tissues may be a result of the relatively more acidic intracellular environment of tumors compared with normal structures, thus inactivating the pH-sensitive enzyme 5-oxoprolinase, which catalyzes the formation of g-glutamyl-Gln dipeptide, an immediate precursor of GSH in the g-glutamyl cycle to glutamate (35). Our data showed that Gln downregulated several enzymes of the g-glutamyl cycle, including 5-oxoprolinase and glutaminase in tumor, but upregulated them in normal tissues (36). The differential effect of Gln on GSH recycling of normal tissues and tumors was associated with a reduction of tumor growth in breast cancer model (19).…”

Section: Discussionmentioning

confidence: 87%

Oral Glutamine Protects against Acute Doxorubicin-Induced Cardiotoxicity of Tumor-Bearing Rats

Тодорова

Kaufmann

Hennings

et al. 2010

The Journal of Nutrition

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Doxorubicin (DOX), a widely used anticancer drug, has a dose-dependent cardiotoxicity, attributed mainly to free radical formation. The cardiomyocyte oxidative stress occurs rapidly after DOX treatment, resulting in harmful modifications to proteins, lipids, and DNA. Previous data showed that oral l-glutamine (Gln) prevented cardiac lipid peroxidation and maintained normal cardiac glutathione (GSH) levels in DOX-treated rats. Our aim in this study was to examine the effect of Gln on DOX-induced cardiac oxidative stress in a tumor-bearing host. Female Fisher344 rats with implanted MatBIII mammary tumors were randomized into 2 groups: a Gln group that received l-Gln (1 g.kg(-1).d(-1)) (n = 10) via a Gln-enriched diet and/or gavage with 50% Gln suspension during the whole experiment and a control group that was fed the same diet formulation without Gln and/or were gavaged with water. All rats received a single injection of 12 mg/kg DOX and were killed 3 d later. GSH levels of hearts, livers, tumors, and blood, as well as cardiac histological alterations, lipid peroxidation, peroxinitrite levels, and caspase-3 activation were determined. Cardiac physiologic alterations were assessed by ultrasound imaging before and 3 d after DOX administration. The Gln supplementation resulted in lower cardiac lipid peroxidation and peroxintrite levels and elevated cardiac catalase enzyme activity and GSH compared with the controls, without affecting those of the tumors. DOX-induced alterations of the echocardiographic parameters were significantly reduced in the Gln-supplemented rats. These data indicate that Gln is able to reduce the oxidative damage of cardiomyocytes that occurs soon after DOX administration and thus protects the heart of a tumor-bearing host from DOX-induced cardiomyopathy.

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“…In implantable sarcoma and breast carcinoma rat models, it was demonstrated that daily oral administration of glutamine results in a 40 % decrease in tumour growth compared to isonitrogenous-fed controls ( 26 ) . Moreover, the data of some studies allow suggestion that dietary supplemental glutamine could be used in the clinical practice to increase the therapeutic index of cancer treatments by protecting normal tissues from, and sensitising tumour cells to, chemotherapy and radiation-related injury ( 27 , 28 ) . Enhancing the antioxidant status of the body and activation of apoptosis exerts chemopreventive effects of glutamine ( 29 ) .…”

Section: Discussionmentioning

confidence: 99%

Total parenteral nutrition in children and adolescents treated with high-dose chemotherapy followed by autologous haematopoietic transplants

et al. 2009

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Total parenteral nutrition (TPN) is still of great importance for haematopoietic stem cell transplantation (HSCT) patients because one of the major adverse effects of the high-dose therapy followed by HSCT is an inadequate oral nutrition intake. The aim of the study was analysis of TPN of young patients in the HSCT period. Twenty-two patients 1·8 -20·8 year-old, median 5·4, treated with high-dose therapy and autologous HSCT because of malignancy were included into the study. Grafts contained 1·35 -7·9 £ 10 The assessment of nutritional condition demonstrated no differences in anthropometric parameters, but increase of serum albumin levels after TPN. Requirement for P 32 was above the normal ranges and correlated positively with platelets reconstitution. Requirement for P 32 and K þ was higher in patients with mucositis than in other patients. Any complications due to TPN were observed. Adequately composed isoenergetic and isonitrogenous TPN with replacement of electrolytes according to their requirement in the early post-transplantation period allows not only improvement in nutritional status of patients but also could contribute to reconstitution of haematopoiesis.Total parenteral nutrition: Autologous haematopoietic transplants: P intake: Haematopoiesis recovery

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Glutamine Affects Glutathione Recycling Enzymes in a DMBA-Induced Breast Cancer Model

Cited by 11 publications

References 43 publications

Control of mammalian gene expression by amino acids, especially glutamine

Control of mammalian gene expression by amino acids, especially glutamine

Oral Glutamine Protects against Acute Doxorubicin-Induced Cardiotoxicity of Tumor-Bearing Rats

Total parenteral nutrition in children and adolescents treated with high-dose chemotherapy followed by autologous haematopoietic transplants

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