Alterations in hexose monophosphate shunt during lymphoblastic transformation

Sagone, Arthur L.; LoBuglio, Albert F.; Balcerzak, Stanley P.

doi:10.1016/0008-8749(74)90195-6

Cited by 59 publications

(34 citation statements)

References 17 publications

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“…However, glycolysis is not the only cellular metabolic pathway that may benefit from increased intracellular glucose levels. The pentose phosphate pathway, which produces pentose sugars required for nucleic acid synthesis and NADPH for reducing power and lipid synthesis, is also upregulated in response to T cell activation (42). In addition, increased glucose metabolism may alter signaling pathways to enhance activation and survival.…”

Section: Discussionmentioning

confidence: 99%

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Jacobs

Herman

MacIver

et al. 2008

The Journal of Immunology

717

766

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T cell activation potently stimulates cellular metabolism to support the elevated energetic and biosynthetic demands of growth, proliferation, and effector function. We show that glucose uptake is limiting in T cell activation and that CD28 costimulation is required to allow maximal glucose uptake following TCR stimulation by up-regulating expression and promoting the cell surface trafficking of the glucose transporter Glut1. Regulation of T cell glucose uptake and Glut1 was critical, as low glucose prevented appropriate T cell responses. Additionally, transgenic expression of Glut1 augmented T cell activation, and led to accumulation of readily activated memory-phenotype T cells with signs of autoimmunity in aged mice. To further examine the regulation of glucose uptake, we analyzed CD28 activation of Akt, which appeared necessary for maximal glucose uptake of stimulated cells and which we have shown can promote Glut1 cell surface trafficking. Consistent with a role for Akt in Glut1 trafficking, transgenic expression of constitutively active myristoylated Akt increased glucose uptake of resting T cells, but did not alter Glut1 protein levels. Therefore, CD28 appeared to promote Akt-independent up-regulation of Glut1 and Akt-dependent Glut1 cell surface trafficking. In support of this model, coexpression of Glut1 and myristoylated Akt transgenes resulted in a synergistic increase in glucose uptake and accumulation of activated T cells in vivo that were largely independent of CD28. Induction of Glut1 protein and Akt regulation of Glut1 trafficking are therefore separable functions of CD28 costimulation that cooperate to promote glucose metabolism for T cell activation and proliferation.

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Section: Discussionmentioning

confidence: 99%

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Jacobs

Herman

MacIver

et al. 2008

The Journal of Immunology

717

766

View full text Add to dashboard Cite

show abstract

“…Treatment of bulk T cells with these mitogens leads to activation similar to antigenic stimulation, including cell growth (blastogenesis) and proliferation, but affecting the majority of T cells in a population, rather than the small number of cells responsive to a specific Ag. Not surprisingly, the energy-demanding processes of mitogenic activation are accompanied by an increase in glucose utilization, detectable within 1 h of stimulation (1,(7)(8)(9).…”

Section: Activation By Mitogens and Aerobic Glycolysismentioning

confidence: 99%

“…Compared with resting cells, actively growing and proliferating cells have increased demand for both pentose sugars and NADPH. T cell stimulation by mitogens activates the pentose phosphate pathway (8). The activity of this pathway peaks by 48 h of stimulation, coinciding with the maximal protein and RNA synthesis of T cell blastogenesis.…”

Section: Activation By Mitogens and Aerobic Glycolysismentioning

confidence: 99%

Regulation of T Lymphocyte Metabolism

Frauwirth

Thompson

2004

The Journal of Immunology

323

191

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Upon stimulation, lymphocytes develop from small resting cells into highly proliferative and secretory cells. Although a great deal of study has focused on the genetic program induced by Ag receptor signals, lymphocytes must also regulate their metabolic function to meet the energetic demands of activation. In this review, we discuss the changes in cellular metabolism that accompany lymphocyte activation, with a particular emphasis on glucose metabolism, a major source of both energy and biosynthetic building blocks. We will also cover the signaling pathways that positively and negatively regulate these changes to maintain metabolic homeostasis in cells that are rapidly growing, dividing, and differentiating.

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“…T cells are dependent on external supplies of glucose to maintain biosynthesis and energy metabolism during activation. Activated T cells adopt a metabolic state of ''aerobic glycolysis'', in which glucose flux through glycolysis is high, but only a small proportion of the glucose is oxidized in mitochondria (Cooper et al, 1963;Culvenor and Weidemann, 1976;Hedeskov, 1968;Roos and Loos, 1970;Sagone et al, 1974). T cell activation is accompanied by a large increase in glucose uptake and glycolysis, which is necessary to support new metabolic demands.…”

Section: (I) Hk Catalyzes the Conversion Of [Glucose To G6p] And [2dgmentioning

confidence: 99%

Evaluation Methods for Facilitative Glucose Transport in Cells and Their Applications

Yamamoto¹,

Ashida

2012

FSTR

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Glucose is used as an energy source in most organisms, from bacteria to humans. The facilitative glucose transport systems are ubiquitous in living cells and are responsible for the movement of glucose across the cell membrane. Since transport of glucose is essential for life and is carefully regulated, glucose uptake assays are performed in a vast number of biological studies. Previously, the method of choice employed radio-labeled hexose derivatives, but now researchers can select several non-radioisotopic methods to evaluate glucose uptake. In the present review, we introduce the various methodologies used to conduct glucose uptake assays and evaluate their application.

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Alterations in hexose monophosphate shunt during lymphoblastic transformation

Cited by 59 publications

References 17 publications

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Regulation of T Lymphocyte Metabolism

Evaluation Methods for Facilitative Glucose Transport in Cells and Their Applications

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