Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

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Red Blood Cells Inhibit Apoptosis of Human Neutrophils

Blood ◽

10.1182/blood.v93.11.4006 ◽

1999 ◽

Vol 93 (11) ◽

pp. 4006-4010 ◽

Cited By ~ 45

Author(s):

Kazutetsu Aoshiba ◽

Yuri Nakajima ◽

Shuji Yasui ◽

Jun Tamaoki ◽

Atsushi Nagai

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Red Blood Cells ◽

Blood Cells ◽

Physical Contact ◽

Glutathione Metabolism ◽

Human Neutrophils ◽

Antioxidant Systems ◽

Neutrophil Apoptosis ◽

Cellular Integrity

Abstract Oxidative stress has been implicated in the triggering of apoptosis in neutrophils. Because red blood cells (RBCs) are well known to scavenge oxidants including H2O2, we tested the hypothesis that RBCs inhibit apoptosis of neutrophils by reducing intracellular oxidative stress. Apoptosis of neutrophils was evaluated by light microscopy and DNA gel electrophoresis. We found that coculture with RBCs protected against neutrophil apoptosis. Neither physical contact between RBCs and neutrophils nor the cellular integrity of RBCs was required to protect against neutrophil apoptosis. Neutrophil apoptosis was promoted by exogenous H2O2 but suppressed by catalase, indicating a role for H2O2 as a mediator of apoptosis. The protective effect of RBCs against apoptosis was due to catalase and glutathione metabolism because blocking of these antioxidant systems in RBCs attenuated the protective effect of RBCs. These results suggest that neutrophils are protected against apoptosis in the circulation.

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Red Blood Cells Inhibit Apoptosis of Human Neutrophils

Blood ◽

10.1182/blood.v93.11.4006.411k18_4006_4010 ◽

1999 ◽

Vol 93 (11) ◽

pp. 4006-4010 ◽

Cited By ~ 3

Author(s):

Kazutetsu Aoshiba ◽

Yuri Nakajima ◽

Shuji Yasui ◽

Jun Tamaoki ◽

Atsushi Nagai

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Red Blood Cells ◽

Blood Cells ◽

Physical Contact ◽

Glutathione Metabolism ◽

Human Neutrophils ◽

Antioxidant Systems ◽

Neutrophil Apoptosis ◽

Cellular Integrity

Oxidative stress has been implicated in the triggering of apoptosis in neutrophils. Because red blood cells (RBCs) are well known to scavenge oxidants including H2O2, we tested the hypothesis that RBCs inhibit apoptosis of neutrophils by reducing intracellular oxidative stress. Apoptosis of neutrophils was evaluated by light microscopy and DNA gel electrophoresis. We found that coculture with RBCs protected against neutrophil apoptosis. Neither physical contact between RBCs and neutrophils nor the cellular integrity of RBCs was required to protect against neutrophil apoptosis. Neutrophil apoptosis was promoted by exogenous H2O2 but suppressed by catalase, indicating a role for H2O2 as a mediator of apoptosis. The protective effect of RBCs against apoptosis was due to catalase and glutathione metabolism because blocking of these antioxidant systems in RBCs attenuated the protective effect of RBCs. These results suggest that neutrophils are protected against apoptosis in the circulation.

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Scanning electron microscopy of erythrophagocytosis by Entamoeba histolytica trophozoites

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012480x ◽

1992 ◽

Vol 50 (1) ◽

pp. 880-881

Author(s):

Victor Tsutsumi ◽

Adolfo Martinez-Palomo ◽

Kyuichi Tanikawa

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Red Blood Cells ◽

Entamoeba Histolytica ◽

Causative Agent ◽

Blood Cells ◽

Protozoan Parasite ◽

Complex Phenomenon ◽

Great Capacity ◽

Scanning Electron

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis in man. The trophozoite or motile form is a highly dynamic and pleomorphic cell with a great capacity to destroy tissues. Moreover, the parasite has the singular ability to phagocytize a variety of different live or death cells. Phagocytosis of red blood cells by E. histolytica trophozoites is a complex phenomenon related with amebic pathogenicity and nutrition.

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Using redox potential as a feasible marker for banked blood quality and the state of oxidative stress in stored red blood cells

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23955 ◽

2021 ◽

Author(s):

Rodney C. Daniels ◽

Hyesun Jun ◽

Robertson D. Davenport ◽

Maryanne M. Collinson ◽

Kevin R. Ward

Keyword(s):

Oxidative Stress ◽

Redox Potential ◽

Red Blood Cells ◽

Blood Cells ◽

The State

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Effect of aspartame on biochemical and oxidative stress parameters in rat blood

Archives of Biological Sciences ◽

10.2298/abs141009016p ◽

2015 ◽

Vol 67 (2) ◽

pp. 535-545 ◽

Cited By ~ 9

Author(s):

Marko Prokic ◽

Milica Paunovic ◽

Milos Matic ◽

Natasa Djordjevic ◽

Branka Ognjanovic ◽

...

Keyword(s):

Oxidative Stress ◽

Red Blood Cells ◽

Blood Cells ◽

Biochemical Parameters ◽

White Blood Cells ◽

Lipid Peroxides ◽

Hdl Cholesterol ◽

Albino Rats ◽

Total Body Mass ◽

Antioxidative Status

Aspartame (ASP) is one of the most widely used nonnutritive sweeteners. This study investigates the chronic effects of ASP on hematological and biochemical parameters, and its effects on the oxidative/antioxidative status in the red blood cells of Wistar albino rats. Rats were provided with ASP (40 mg/kg/daily for six weeks) in drinking water. Increased food and fluid intake was observed in the ASP-treated rats. Total body mass was significantly decreased in the ASP-treated rats. Treatment with ASP caused an increase in the concentrations of glucose, cholesterol, LDL-cholesterol, and in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as a decrease in the levels of HDL-cholesterol in the serum. A significant decline in the number of white blood cells (WBC) was observed after ASP uptake. Based on the results we conclude that ASP induces oxidative stress, observed as an alteration of the glutathione redox status, which leads to increased concentrations of nitric oxide (NO) and lipid peroxides (LPO) in the red blood cells. Changes in biochemical parameters, lipid metabolism, as well as changes in the levels of oxidative stress markers and the appearance of signs of liver damage indicate that chronic use of ASP can lead to the development of hyperglycemia, hypercholesterolemia and associated diseases.

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Using Redox Potential as a Feasible Marker for Banked Blood Quality and the State of Oxidative Stress in Stored Red Blood Cells

10.21203/rs.3.rs-104378/v1 ◽

2020 ◽

Author(s):

Rodney C Daniels ◽

Hyesun Jun ◽

Robertson D Davenport ◽

Maryanne M Collinson ◽

Kevin R Ward

Keyword(s):

Oxidative Stress ◽

Redox Potential ◽

Red Blood Cells ◽

Healthy Volunteers ◽

Blood Cells ◽

Storage Time ◽

Cell Function ◽

Venous Blood ◽

Functional Changes ◽

Over Time

Abstract Background Stored Red Blood Cells (RBCs) may undergo oxidative stress over time, with functional changes affecting critical tasks such as oxygen delivery. Central to these changes are oxidation-reduction (redox) reactions and the redox potential (RP) that must be maintained for proper cell function. RP imbalance can lead to oxidative stress that may contribute to storage lesions and transfusion-related morbidities. Direct measures of RP may allow for evaluation of erythrocyte quality and enable corrections of RP prior to transfusion. Methods Multiple random RBC segments were tested, ranging in age from 5 to 40 days at 5 day intervals. RP was recorded by measuring open circuit potential of RBCs using novel nanoporous gold electrodes with Ag/AgCl reference. RP measures were also performed on peripheral venous blood samples from 10 healthy volunteers. RP measures were compared between groups of aged RBCs, and with volunteer blood. Results Stored RBCs show time-dependent increases in RP. There were significant differences in Day 5 RP compared to all other groups (p≤0.005), Day 10-15 vs ages ≥ Day 20 (p≤0.025), Day 20-25 vs Day 40 (p=0.039), and all groups compared to healthy volunteers. RP became more positive over time suggesting ongoing oxidation as RBCs age. However, storage time alone does not predict the ultimate RP value measured from a given unit.Conclusions There are significant differences in RP between freshly stored RBCs and all others, with RP becoming more positive over time. However, storage time alone does not predict RP, indicating RP screening may be important independent of storage time and may serve as a marker of RBC quality and state of oxidative stress. RP measurements may also provide a target by which to restore RP balance in aged pRBCs, improving their clinical effectiveness while reducing associated morbidities.

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Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis

BioMed Research International ◽

10.1155/2015/616834 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 34

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Rachele Riganò

Keyword(s):

Oxidative Stress ◽

Immune System ◽

Red Blood Cells ◽

Immune Cells ◽

Blood Cells ◽

Atherosclerotic Disease ◽

Intraplaque Hemorrhage ◽

Immune System Activation ◽

Adaptive Immune Cells ◽

The Impact

Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs) accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.

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