Increased Uptake and Accumulation of Vitamin C in Human Immunodeficiency Virus 1-infected Hematopoietic Cell Lines

Rivas, Coralia I.; Vera, Juan Carlos; Guaiquil, Victor H.; Velásquez, Fernando V.; Bórquez-Ojeda, Oriana; Cárcamo, Juan G.; Concha, Ilona I.; Golde, David W.

doi:10.1074/jbc.272.9.5814

Cited by 28 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ascorbic acid is known to increase the accessibility and absorption of iron from non-heme iron sources [4]. Vitamin C has been demonstrated to kill HIV-positive cells and help HIV-positive individuals by increasing the immune system [5]. Vitamin C significantly decreases the adverse effect of reactive species such as reactive oxygen and nitrogen that can cause oxidative damage to macromolecules such as lipids, DNA and proteins [6].…”

Section: Introductionmentioning

confidence: 99%

Uv-Vis, NMR and Ft-Ir Spectra of Tautomers of Vitamin C. Experimental and DFT Calculations

Dabbagh

Azami

Farrokhpour

et al. 2014

J. Chil. Chem. Soc.

View full text Add to dashboard Cite

Experimental and computational analysis of spectroscopic parameters of L-ascorbic acid (vitamin C) and its tautomers was investigated by Density Functional Theory (DFT) using B3LYP method. The optimized geometries and calculated vibrational frequencies were evaluated. The latter was compare with those of experimental values. The λ max values of L-ascorbic acid were found 259 (at pH = 3) experimentally, 238 and 247 nm calculated in the gas and water phase at TD-DFT methods, respectively.

show abstract

Section: Introductionmentioning

confidence: 99%

Uv-Vis, NMR and Ft-Ir Spectra of Tautomers of Vitamin C. Experimental and DFT Calculations

Dabbagh

Azami

Farrokhpour

et al. 2014

J. Chil. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…Alternatively, this difference may be due to that HL60 and U937 cells may express other GLUT transporters and these GLUTs may bind resveratrol with lower affinity. Literature data shows that besides the abundant expression of GLUT1 no reactivity was observed with anti-GLUT2, -GLUT3, -GLUT4, or -GLUT5 antibodies in HL60 (65) or U937 cells (48). However, there are no data regarding the expression of GLUT6 -12 on these cells, so we cannot dismiss the possibility that HL60 or U937 cells express some of these GLUT transporters and that these GLUTs may bind resveratrol with lower affinity.…”

Section: Discussionmentioning

confidence: 79%

“…Short uptake assays enabled us to carry out a detailed kinetic analysis of the transport of 2DG as distinct from the accumulation of the hexose. Both HL-60 and U-937 cell lines express mainly GLUT1 (48,65), and only one saturable component of substrate transport was detected on either cell line, with K m values of 2.5-8.5 mM, as expected from the functional properties of GLUT1 (38,39,65). Resveratrol inhibited glucose transport in both cells, which demonstrated that the deleterious effect of the phytoalexin on glucose uptake could be validated in different human cells, providing convincing evidence that resveratrol affects the functional activity of GLUT1 in a manner independent of the cellular environment in which the transporter is expressed.…”

Section: Discussionmentioning

confidence: 99%

Resolution of the direct interaction with and inhibition of the human GLUT1 hexose transporter by resveratrol from its effect on glucose accumulation

Salas

Obando

Ojeda

et al. 2013

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

Salas M, Obando P, Ojeda L, Ojeda P, Pérez A, VargasUribe M, Rivas CI, Vera JC, Reyes AM. Resolution of the direct interaction with and inhibition of the human GLUT1 hexose transporter by resveratrol from its effect on glucose accumulation. Am J Physiol Cell Physiol 305: C90 -C99, 2013. First published April 24, 2013; doi:10.1152/ajpcell.00387.2012.-Resveratrol acts as a chemopreventive agent for cancer and as a potential antiobesity and antidiabetic compound, by leading to reduced body fat and improved glucose homeostasis. The exact mechanisms involved in improving hyperglycemic state are not known, but most of the glucose uptake into mammalian cells is facilitated by the GLUT hexose transporters. Resveratrol is structurally similar to isoflavones such as genistein, which inhibit the glucose uptake facilitated by the GLUT1 hexose transporter. Here we examined the direct effects of resveratrol on glucose uptake and accumulation in HL-60 and U-937 leukemic cell lines, which express mainly GLUT1, under conditions that discriminate transport from the intracellular substrate phosphorylation/ accumulation. Resveratrol blocks GLUT1-mediated hexose uptake and thereby affects substrate accumulation on these cells. Consequently, we characterized the mechanism involved in inhibition of glucose uptake in human red cells. Resveratrol inhibits glucose exit in human red cells, and the displacement of previously bound cytochalasin B revealed the direct interaction of resveratrol with GLUT1. Resveratrol behaves as a competitive blocker of glucose uptake under zero-trans exit and exchange kinetic assays, but it becomes a mixed noncompetitive blocker when zero-trans entry transport was assayed, suggesting that the binding site for resveratrol lies on the endofacial face of the transporter. We propose that resveratrol interacts directly with the human GLUT1 hexose transporter by binding to an endofacial site and that this interaction inhibits the transport of hexoses across the plasma membrane. This inhibition is distinct from the effect of resveratrol on the intracellular phosphorylation/accumulation of glucose. glucose transport; GLUT1 transporter; hexose uptake; leukemic cells; resveratrol CANCER CELLS PRODUCE ENERGY predominantly via the anaerobic degradation of glucose. This process, which occurs even in the presence of high concentration of oxygen, assures the high rate of proliferation of cancer cells (67). Recent evidence indicates that the rapid breakdown of glucose through both the glycolytic and pentose phosphate pathways provides not only a quick source of energy but also an immediate supply of metabolites intermediates that will finally feed the biosynthetic pathways (13,24,61). Consistently, the consumption of glucose in cancer cells is significantly enhanced compared with normal cells, indicating that glucose plays a key role in the survival of cancer cells (12,20,25). Indeed, cancer cells are sensitive to glucose deprivation, as limiting the supply of glucose prevents cell proliferation and induces apoptosis (4,36,...

show abstract

“…upon treatment with large doses of ascorbate (based on bowel tolerance), he noted that vitamin c was more rapidly metabolized depending on the severity of the disease, thus necessitating a higher vitamin c dosage (15). ascorbate has been demonstrated to kill HiV directly in both blood and culture medium (22), and preferentially lessens the viability of HiV-infected cells to reproduce or survive (23). ascorbate has also been shown to improve the clinical status of HiV-infected patients, such as those who develop myopathy secondary to azT therapy (24), and to lower oxidative stress (16).…”

Section: Discussionmentioning

confidence: 99%

Micronutrient cooperation in the suppression of HIV production in chronically and latently infected cells

Jariwalla

Gangapurkar²,

Pandit³

et al. 2010

Mol Med Rep

View full text Add to dashboard Cite

Abstract. nutrients are known to display pharmacologic activity against viruses and to exert cooperative effects in cells. To study the influence of nutrient cooperation on HiV production in chronically infected T lymphocytes, we evaluated the individual and combined effects of nutrients on HiV-1 reverse transcriptase (rT) released into the culture supernatant. in unstimulated cells, low concentrations of single nutrients, namely ascorbic acid (aa), green tea polyphenols (GT) or lysine, did not significantly suppress HiV-1 rT production. However, when GT (25 µg/ml) and aa (32-64 µg/ml) were combined and applied to cells, extracellular RT was significantly reduced relative to the control. combining GT (25 µg/ml) with lysine (25 µg/ml) also reduced the rT level to a greater extent (51% of control) than was observed wih lysine alone, and the addition of aa (16 µg/ml) to the combination further decreased rT to 17% of the control (p=0.06). under the same assay conditions, the nucleoside analog azidothymidine did not significantly suppress HiV production at low to moderate concentrations (0.5-1.0 µg/ml), but did reduce the rT level to 40% of the control (p=0.02) at the highest dose tested (2 µg/ml). in unstimulated cells as well as in latently infected cells stimulated with mitogen (PMa or TnF-α), a nutrient mixture containing GT, AA and amino acids imparted significantly greater rT suppression than equivalent concentrations of key individual components. nutrient effects on rT suppression were virus-specific and were not due to non-specific cellular toxicity. These results suggest that relatively non-toxic micronutrient combinations are more potent than single nutrients in suppressing virus production in chronically infected T cells, indicating that the constituent nutrients have a cooperative effect in HiV inhibition.

show abstract

Increased Uptake and Accumulation of Vitamin C in Human Immunodeficiency Virus 1-infected Hematopoietic Cell Lines

Cited by 28 publications

References 41 publications

Uv-Vis, NMR and Ft-Ir Spectra of Tautomers of Vitamin C. Experimental and DFT Calculations

Uv-Vis, NMR and Ft-Ir Spectra of Tautomers of Vitamin C. Experimental and DFT Calculations

Resolution of the direct interaction with and inhibition of the human GLUT1 hexose transporter by resveratrol from its effect on glucose accumulation

Micronutrient cooperation in the suppression of HIV production in chronically and latently infected cells

Contact Info

Product

Resources

About