Oxidant injury of caucasian glucose-6-phosphate dehydrogenase—deficient red blood cells by phagocytosing leukocytes during infection

Baehner, Robert L.; Nathan, David G.; Castle, W. E.

doi:10.1172/jci106747

Cited by 88 publications

(35 citation statements)

References 32 publications

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“…In turn, NADPH is (1) a key intracellular reducing equivalent by maintaining glutathione in the reduced form, 127 (2) a cofactor utilized by eNOS to generate NO • , 128 and (3) a key participant in the maintenance of normal BH4 levels via the dihydrofolate reductase salvage pathway. 129 Long recognized as the primary mechanism by which to account for oxidative injury in erythrocytes, 130 impaired G6PD activity has also been linked to a swathe of other pathobiological processes, including diminished eNOS expression and activity that results in vascular endothelial dysfunction, 128 progressive myocardial dysfunction in response to ischemiareperfusion injury, 131 pulmonary hypertension, 132 and renal dysfunction with albuminuria. 133 Endothelial cell migration and angiogenesis are also G6PD-dependent processes because enzyme deficiency is linked to diminished VEGF-dependent angiogenesis via decreased eNOS phosphorylation.…”

Section: Antioxidant Enzymes and The Cellular Redox Potentialmentioning

confidence: 99%

Subcellular Localization of Oxidants and Redox Modulation of Endothelial Nitric Oxide Synthase

Maron

Michel

2012

Circ J

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Reactive oxygen species (ROS) have long been viewed as deleterious chemicals that lead to oxidative stress. More recently, ROS, especially the stable ROS hydrogen peroxide (H2O2), have been shown to have roles in normal physiological responses in vascular cells. Endothelial nitric oxide synthase (eNOS) is dynamically targeted to plasmalemmal caveolae, and represents the principal enzymatic source of nitric oxide (NO • ) in the vascular wall. eNOS maintains normal vascular tone and inhibits the clinical expression of many cardiovascular diseases. Increases in oxidative stress are associated with eNOS dysfunction. In a paradigm shift in the conceptual framework linking redox biochemistry and vascular function, H2O2 has been established as a physiological mediator in signaling pathways, yet the intracellular sources of H2O2 and their regulation remain incompletely understood. The subcellular distributions of ROS and of ROS-modified proteins critically influence the redox-sensitive regulation of eNOS-dependent pathways. ROS localization in specific subcellular compartments can lead to selective oxidative modifications of eNOS and eNOS-associated proteins. Likewise, the dynamic targeting of eNOS and other signaling proteins influences their interactions with reactive nitrogen species and ROS that are also differentially distributed within the cell. Thus, the subcellular distribution both of eNOS and redox-active biomolecules serves as a critical basis for the control of the "redox switch" that influences NO• - and oxidant-regulated signaling pathways. Here we discuss the biochemical factors, cellular determinants, and molecular mechanisms that modulate redox-sensitive regulation of eNOS and NO tion of eNOS is dynamically regulated 9 and the enzyme is thus exposed to different concentrations of ROS depending upon where in the cell the protein is localized. Alterations in eNOS function due to changes in ROS levels may reflect either physiological or pathological responses in both normal cells and in vascular disease states. The relationship between impaired eNOS activity and the development of vascular dysfunction has been extensively studied: NO • is a potent vasodilator molecule that also attenuates platelet aggregation, vascular smooth muscle cell (VSMC) proliferation, and negative vascular remodeling. 10 Collectively, these properties contribute to the prevention of intermediate pathophenotypes of vascular disease, including cardiac and/or vascular hypertrophy, fibrosis, and atherosclerosis. In counterpoise to these deleterious effects of ROS, there also appears to be a key physiological role for H2O2 in eNOS regulation. 11 Elucidating the redoxdependent mechanisms involved in the physiological and pathophysiological regulation of eNOS by ROS will provide critical new insights into vascular disease states and may lead to the identification of novel treatment targets related to eNOS and eNOS-modulated vascular responses.

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Section: Antioxidant Enzymes and The Cellular Redox Potentialmentioning

confidence: 99%

Subcellular Localization of Oxidants and Redox Modulation of Endothelial Nitric Oxide Synthase

Maron

Michel

2012

Circ J

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“…Hydrogen peroxide is generated by activated polymorphonuclear neutrophils. 24 Based on studies of the effect of fractionated extracts on erythrocyte metabolism, the toxic components of fava beans have been suggested to be the pyrimidine aglycones, divicine and isouramil25 '26 …”

Section: Mechanism Ofhaemolysismentioning

confidence: 99%

Glucose-6-phosphate dehydrogenase deficiency

Mehta

Mason

Vulliamy

2000

Best Practice & Research Clinical Haematology

202

139

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“…H2O2 can be produced in an excess in normal polymorphonuclear leukocytes during phagocytosis and be released and may act on glucose-6-phosphate dehydro genase-deficient erythrocytes as an oxidant stress to cause a decrease of the reduced glutathione level and hemolysis, as demonstrated by Baehner et al (1971 Younkin et al (1971) have studied on the mechanism of the hydrogen peroxide hemolysis and its reversal with phenols. They have suggested that lipid peroxida tion causes hemolysis through membrane damage resulting in colloid osmotic lysis , and that vitamin E prevents H2O2 induced hemolysis by acting as a phenolic antioxidant, which is capable of neutralizing free radicals and thereby terminates chain reaction-type lipid peroxidation.…”

Section: Effects Of Vitamin E-nicotinate On the Lipid Peroxidation Ofmentioning

confidence: 99%

Effects of Vitamin E on the Aggregation and the Lipid Peroxidation of Platelets Exposed to Hydrogen Peroxide

Higashi

Kikuchi

1974

Tohoku J. Exp. Med.

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Oxidant injury of caucasian glucose-6-phosphate dehydrogenase—deficient red blood cells by phagocytosing leukocytes during infection

Cited by 88 publications

References 32 publications

Subcellular Localization of Oxidants and Redox Modulation of Endothelial Nitric Oxide Synthase

Subcellular Localization of Oxidants and Redox Modulation of Endothelial Nitric Oxide Synthase

Glucose-6-phosphate dehydrogenase deficiency

Effects of Vitamin E on the Aggregation and the Lipid Peroxidation of Platelets Exposed to Hydrogen Peroxide

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