Low Glutamine Concentrations Induce Phenotypical and Functional Differentiation of U937 Myelomonocytic Cells ,

Dietary copper (Cu) deficiency impairs both innate and acquired branches of immunity. Specific roles of Cu in the activation and effector activities of host-defense cells remain largely unknown. The effects of Cu status on effector activities of a monocytic cell line were investigated as an initial step in the elucidation of specific functions of Cu in phagocytic cells. Exposure of differentiating U937 human promonocytic cells to 5 mol/L 2,3,2-tetraamine (tet), a high affinity Cu chelator, for 4 d decreased cellular Cu by 62% without altering cellular Cu,Zn-superoxide dismutase (SOD) activity, Zn content, mitochondrial activity and protein synthesis. In contrast, Cu deficiency suppressed the respiratory burst activity and markedly compromised the ability of U937 cells to kill Salmonella. Similarly, treatment of RAW264.7 murine macrophages with 5 mol/L tet decreased cell Cu by 78% and Cu,Zn-SOD activity by 15% and increased bacterial survival by 180%. The tet-induced impairment of respiratory burst and bactericidal activities was blocked in cultures supplemented with Cu, but not Zn or Fe. In addition, lipopolysaccharide (LPS)-induced secretion of the inflammatory mediators, tumor necrosis factor-␣, interleukin (IL)-1␤, IL-6 and prostaglandin E 2 (PGE 2 ), was decreased by 30 -60% in tet-treated U937 cells. Flow cytometric analysis of the surface antigens CD11b and CD71 showed that the suppressed activities of Cu-deficient cells were not due to an attenuation in the degree of differentiation or secondary iron deficiency. These data demonstrate that U937 cells provide a useful model for examining the biochemical roles of Cu in monocyte activity. J. Nutr. 130: 1536Nutr. 130: -1542Nutr. 130: , 2000

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“…Cell cycle analysis was determined using propidium iodidestained cells as described by Spittler et al (1997a).…”

Section: Methodsmentioning

confidence: 99%

Copper Deficiency Suppresses Effector Activities of Differentiated U937 Cells

Huang

Failla

2000

The Journal of Nutrition

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“…(Reitzer et al 1979;Rossignol et al 2004). Withdrawal of glutamine reduces cell proliferation and induces cell differentiation (Spittler et al 1997). A prerequsite of glutaminolysis is the over-expression of glutaminase, the first enzyme within the glutaminolytic pathway.…”

Section: The Role Of Glutaminolysis For Endothelial Cell Proliferatiomentioning

confidence: 99%

Premature senescence of human endothelial cells induced by inhibition of glutaminase

et al. 2008

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Cellular senescence is now recognized as an important mechanism of tumor suppression, and the accumulation of senescent cells may contribute to the aging of various human tissues. Alterations of the cellular energy metabolism are considered key events in tumorigenesis and are also known to play an important role for aging processes in lower eukaryotic model systems. In this study, we addressed senescence-associated changes in the energy metabolism of human endothelial cells, using the HUVEC model of in vitro senescence. We observed a drastic reduction in cellular ATP levels in senescent endothelial cells. Although consumption of glucose and production of lactate significantly increased in senescent cells, no correlation was found between both metabolite conversion rates, neither in young endothelial cells nor in the senescent cells, which indicates that glycolysis is not the main energy source in HUVEC. On the other hand, glutamine consumption was increased in senescent HUVEC and inhibition of glutaminolysis by DON, a specific inhibitor of glutaminase, led to a significant reduction in the proliferative capacity of both early passage and late passage cells. Moreover, inhibition of glutaminase activity induced a senescent-like phenotype in young HUVEC within two passages. Together, the data indicate that glutaminolysis is an important energy source in endothelial cells and that alterations in this pathway play a role in endothelial cell senescence.

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“…A high capacity of glutaminolysis is linked to neoplastic transformation. An inhibition of glutaminolysis decreases tumor cell proliferation and correlates with phenotypical and functional differentiation of the cells (Lobo et al 2000;Spittler et al 1997). Besides the regeneration of energy, glutamine catabolism provides glutamate and aspartate, which, together with glutamine itself, are precursors of nucleic acid and serine synthesis.…”

Section: Alternative To Glycolytic Energy Conversionmentioning

confidence: 99%

Robust metabolic adaptation underlying tumor progression

2008

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Tumor metabolism represents the end point of many signal cascades recruited by oncogenic activation. Energy metabolism of cancer cells attracted the attention of biochemists over eight decades ago. For example, high consume of glucose and high lactate production under aerobic conditions make up one of the most fundamental characteristics of cancer cells and has been exploited for diagnosis. At the same time, study of the metabolic status of tumor cells during tumor progression reveals characteristic adaptations during carcinogenesis. Although these metabolic adaptations are not the main defects that cause cancer, they may confer advantages to survive. In this review, we discuss the main metabolic hot spots and their relationship with main tumor progression events. An accurate metabolic map of the many tumor phenotypes could offer new options in the treatment of cancer.Keywords Tumor metabolism Á Warburg effect Á Regulation of glucose metabolism in tumors Á Acidosis and tumor progression Á Biosynthetic pathways in tumoral metabolism Á Alternative to glycolytic energy conversion Á Isoenzyme expression in tumor cells Á Tumor metabolism and apoptosis1 Introduction

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Low Glutamine Concentrations Induce Phenotypical and Functional Differentiation of U937 Myelomonocytic Cells ,

Cited by 39 publications

References 28 publications

Copper Deficiency Suppresses Effector Activities of Differentiated U937 Cells

Copper Deficiency Suppresses Effector Activities of Differentiated U937 Cells

Premature senescence of human endothelial cells induced by inhibition of glutaminase

Robust metabolic adaptation underlying tumor progression

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