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1.
Biomolecules ; 13(8)2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37627327

RESUMO

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases. In this review, we discuss the most relevant oxidant species involved in RBC damage, the enzymatic and low molecular weight antioxidant systems that protect RBCs against oxidative injury, and finally, the role of oxidative stress in different red cell diseases, including sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency, highlighting the underlying mechanisms leading to pathological RBC phenotypes.


Assuntos
Anemia Hemolítica Congênita não Esferocítica , Anemia Falciforme , Humanos , Antioxidantes , Eritrócitos , Estresse Oxidativo
2.
ACS Omega ; 8(1): 147-168, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643550

RESUMO

Red blood cells (RBCs) are exposed to both external and internal sources of oxidants that challenge their integrity and compromise their physiological function and supply of oxygen to tissues. Autoxidation of oxyhemoglobin is the main source of endogenous RBC oxidant production, yielding superoxide radical and then hydrogen peroxide. In addition, potent oxidants from other blood cells and the surrounding endothelium can reach the RBCs. Abundant and efficient enzymatic systems and low molecular weight antioxidants prevent most of the damage to the RBCs and also position the RBCs as a sink of vascular oxidants that allow the body to maintain a healthy circulatory system. Among the antioxidant enzymes, the thiol-dependent peroxidase peroxiredoxin 2, highly abundant in RBCs, is essential to keep the redox balance. A great part of the RBC antioxidant activity is supported by an active glucose metabolism that provides reducing power in the form of NADPH via the pentose phosphate pathway. There are several RBC defects and situations that generate oxidative stress conditions where the defense mechanisms are overwhelmed, and these include glucose-6-phosphate dehydrogenase deficiencies (favism), hemoglobinopathies like sickle cell disease and thalassemia, as well as packed RBCs for transfusion that suffer from storage lesions. These oxidative stress-associated pathologies of the RBCs underline the relevance of redox balance in these anucleated cells that lack a mechanism of DNA-inducible antioxidant response and rely on a complex and robust network of antioxidant systems.

3.
J Biol Chem ; 298(1): 101503, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34929164

RESUMO

Hydrogen peroxide (H2O2) not only is an oxidant but also is an important signaling molecule in vascular biology, mediating several physiological functions. Red blood cells (RBCs) have been proposed to be the primary sink of H2O2 in the vasculature because they are the main cellular component of blood with a robust antioxidant defense and a high membrane permeability. However, the exact permeability of human RBC to H2O2 is neither known nor is it known if the mechanism of permeation involves the lipid fraction or protein channels. To gain insight into the permeability process, we measured the partition constant of H2O2 between water and octanol or hexadecane using a novel double-partition method. Our results indicated that there is a large thermodynamic barrier to H2O2 permeation. The permeability coefficient of H2O2 through phospholipid membranes containing cholesterol with saturated or unsaturated acyl chains was determined to be 4 × 10-4 and 5 × 10-3 cm s-1, respectively, at 37 °C. The permeability coefficient of human RBC membranes to H2O2 at 37 °C, on the other hand, was 1.6 × 10-3 cm s-1. Different aquaporin-1 and aquaporin-3 inhibitors proved to have no effect on the permeation of H2O2. Moreover, human RBCs devoid of either aquaporin-1 or aquaporin-3 were equally permeable to H2O2 as normal human RBCs. Therefore, these results indicate that H2O2 does not diffuse into RBCs through aquaporins but rather through the lipid fraction or a still unidentified membrane protein.


Assuntos
Aquaporinas , Membrana Eritrocítica , Eritrócitos , Peróxido de Hidrogênio , Aquaporinas/metabolismo , Permeabilidade da Membrana Celular , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Humanos , Peróxido de Hidrogênio/sangue , Peróxido de Hidrogênio/farmacocinética , Metabolismo dos Lipídeos
4.
Adv Exp Med Biol ; 1127: 3-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140168

RESUMO

This chapter includes an overview of the structure of cell membranes and a review of the permeability of membranes to biologically relevant oxygen and nitrogen reactive species, namely oxygen, singlet oxygen, superoxide, hydrogen peroxide, hydroxyl radical, nitric oxide, nitrogen dioxide, peroxynitrite and also hydrogen sulfide. Physical interactions of these species with cellular membranes are discussed extensively, but also their relevance to chemical reactions such as lipid peroxidation. Most of these species are involved in different cellular redox processes ranging from physiological pathways to damaging reactions against biomolecules. Cell membranes separate and compartmentalize different processes, inside or outside cells, and in different organelles within cells. The permeability of these membranes to reactive species varies according to the physicochemical properties of each molecule. Some of them, such as nitric oxide and oxygen, are small and hydrophobic and can traverse cellular membranes virtually unhindered. Nitrogen dioxide and hydrogen sulfide find a slightly higher barrier to permeation, but still their diffusion is largely unimpeded by cellular membranes. In contrast, the permeability of cellular membranes to the more polar hydrogen peroxide, is up to five orders of magnitude lower, allowing the formation of concentration gradients, directionality and effective compartmentalization of its actions which can be further regulated by specific aquaporins that facilitate its diffusion through membranes. The compartmentalizing effect on anionic species such as superoxide and peroxynitrite is even more accentuated because of the large energetic barrier that the hydrophobic interior of membranes presents to ions that may be overcome by protonation or the use of anion channels. The large difference in cell membrane permeability for different reactive species indicates that compartmentalization is possible for some but not all of them.


Assuntos
Permeabilidade da Membrana Celular , Membrana Celular/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Difusão , Óxido Nítrico , Oxirredução , Superóxidos
5.
Free Radic Biol Med ; 121: 231-239, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29753074

RESUMO

Red blood cells (RBC) are considered as a circulating sink of H2O2, but a significant debate remains over the role of the different intraerythocyte peroxidases. Herein we examined the kinetic of decomposition of exogenous H2O2 by human RBC at different cell densities, using fluorescent and oxymetric methods, contrasting the results against a mathematical model. Fluorescent measurements as well as oxygen production experiments showed that catalase was responsible for most of the decomposition of H2O2 at cell densities suitable for both experimental settings (0.1-10â€¯× 1010 cell L-1), since sodium azide but not N-ethylmaleimide (NEM) inhibited H2O2 consumption. Oxygen production decreased at high cell densities until none was detected above 1.1 × 1012 cell L-1, being recovered after inhibition of the thiol dependent systems by NEM. This result underlined that the consumption of H2O2 by catalase prevail at RBC densities regularly used for research, while the thiol dependent systems predominate when the cell density increases, approaching the normal number in blood (5â€¯× 1012 cell L-1). The mathematical model successfully reproduced experimental results and at low cell number it showed a time sequence involving Prx as the first line of defense, followed by catalase, with a minor role by Gpx. The turning points were given by the total consumption of reduced Prx in first place and reduced GSH after that. However, Prx alone was able to account for the added H2O2 (50 µM) at physiological RBC density, calling attention to the importance of cell density in defining the pathway of H2O2 consumption and offering an explanation to current apparently conflicting results in the literature.


Assuntos
Catalase/metabolismo , Eritrócitos/metabolismo , Peróxido de Hidrogênio/metabolismo , Modelos Teóricos , Oxidantes/metabolismo , Oxigênio/metabolismo , Peroxidases/metabolismo , Humanos , Cinética
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