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1.
Chem Biol Interact ; 319: 109019, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32092302

RESUMO

The inhibition of the enzyme acetylcholinesterase (AChE) is a frequently used therapeutic option to treat Alzheimer's disease (AD). By decreasing the levels of acetylcholine degradation in the synaptic space, some cognitive functions of patients suffering from this disease are significantly improved. Rivastigmine is one of the most widely used AChE inhibitors. The objective of this work was to determine the effects of this drug on human erythrocytes, which have a type of AChE in the cell membrane. To that end, human erythrocytes and molecular models of its membrane constituted by dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were used. They correspond to classes of phospholipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively. The experimental results obtained by X-ray diffraction and differential scanning calorimetry (DSC) indicated that rivastigmine molecules were able to interact with both phospholipids. Fluorescence spectroscopy results showed that rivastigmine produce a slight change in the acyl chain packing order and a weak displacement of the water molecules of the hydrophobic-hydrophilic membrane interface. On the other hand, observations by scanning electron microscopy (SEM) showed that the drug changed the normal biconcave shape of erythrocytes in stomatocytes (cup-shaped cells) and echinocytes (speculated shaped).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Eritrócitos/efeitos dos fármacos , Rivastigmina/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Varredura Diferencial de Calorimetria/métodos , Forma Celular/efeitos dos fármacos , Dimiristoilfosfatidilcolina/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Humanos , Microscopia Eletrônica de Varredura/métodos , Modelos Moleculares , Fosfatidiletanolaminas/metabolismo , Fosfolipídeos/metabolismo , Espectrometria de Fluorescência/métodos , Difração de Raios X/métodos
2.
Curr Diabetes Rev ; 16(2): 143-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30451115

RESUMO

INTRODUCTION: The Diabetes Prevention Program study results indicated that metformin therapy was not as beneficial as a lifestyle modification for delaying the development of type 2 diabetes in individuals at high risk of the disease. A key feature in the etiology of type 2 diabetes mellitus, which appears in the prediabetic phase, is a significant deficiency, compared to healthy controls, in highly flexible poly-cis-unsaturated fatty acyl chains in membrane phospholipids. This deficiency lowers membrane flexibility, which in turn, reduces the amount of all functional Class I glucose transporters, and thereby reduces glucose-mediated ATP production. This leads to an increase in essentially saturated free fatty acid (FFA) levels for fatty-acid-mediated ATP production, which will set up a vicious cycle of raising the levels of essentially saturated FFAs and lowering the level of transmembrane glucose transport. Metformin suppresses hepatic gluconeogenesis, which reduces the plasma glucose concentration. CONCLUSION: We hypothesize that chronic metformin treatment leads to an additional increase in essentially saturated FFAs, which causes an additional rise in membrane stiffness and hypoxia. So we propose that all these metformin-mediated activities accelerated the onset of type 2 diabetes in the participants of the metformin group in the Diabetes Prevention Program study, compared to the participants of the lifestyle-intervention group in this study. We propose that the biochemical reactions, involved in the fatty-acid-mediated ATP production, play an important part in the increase of the observed essentially saturated FFA concentrations. These statements should also extend to the metformin therapy of individuals with type 2 diabetes.


Assuntos
Membrana Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos/metabolismo , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Estado Pré-Diabético/metabolismo , Glicemia/metabolismo , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Progressão da Doença , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Estilo de Vida Saudável , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/terapia , Medição de Risco , Fatores de Risco
3.
J Biol Phys ; 45(4): 367-377, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31758351

RESUMO

The intensity of erythrocyte membrane fluctuations was studied by laser interference microscopy (LIM), which provide information about mechanical properties of the erythrocyte membrane. Atomic force microscopy (AFM) was used to study erythrocyte surface relief; it is related to the cytoskeleton structure of erythrocyte membrane. Intact human erythrocytes and erythrocytes with a destroyed cytoskeleton were used. According to the obtained results, cytoskeleton damage induced by heating up to 50 °Ð¡ results in a reduced intensity of cell membrane fluctuations compared to non-treated cells (20.6 ± 10.2 vs. 30.5 ± 5.5 nm, correspondingly), while the roughness of the membrane increases (4.5 ± 1.5 vs. 3.4 ± 0.5 nm, correspondingly).


Assuntos
Citoesqueleto/metabolismo , Membrana Eritrocítica/metabolismo , Eritrócitos/citologia , Temperatura Alta/efeitos adversos , Fenômenos Mecânicos , Fenômenos Biomecânicos
4.
Commun Biol ; 2: 350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552303

RESUMO

Red blood cells (RBCs) play a critical role in oxygen transport, and are the focus of important diseases including malaria and the haemoglobinopathies. Proteins at the RBC surface can determine susceptibility to disease, however previous studies classifying the RBC proteome have not used specific strategies directed at enriching cell surface proteins. Furthermore, there has been no systematic analysis of variation in abundance of RBC surface proteins between genetically disparate human populations. These questions are important to inform not only basic RBC biology but additionally to identify novel candidate receptors for malarial parasites. Here, we use 'plasma membrane profiling' and tandem mass tag-based mass spectrometry to enrich and quantify primary RBC cell surface proteins from two sets of nine donors from the UK or Senegal. We define a RBC surface proteome and identify potential Plasmodium receptors based on either diminished protein abundance, or increased variation in RBCs from West African individuals.


Assuntos
Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Proteínas de Membrana/metabolismo , Proteômica , Humanos , Proteoma , Proteômica/métodos , Biologia de Sistemas/métodos
5.
Bull Exp Biol Med ; 167(4): 508-511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31494762

RESUMO

The effect of H2S on changes in erythrocyte volume was studied by spectrophotometrical and potentiometric methods. It was found that H2S donor NaHS (2.5, 10, and 100 µM) induced an increase in erythrocyte volume in heterosmotic media. Activation of Gardos channels with A23187 or ascorbate-phenazine methosulfate system causes erythrocyte shrinkage and hyperpolarization of their membrane, while addition of NaHS restored erythrocyte volume. The decrease in erythrocyte volume upon blockade of Na+,K+,2Cl- cotransporter (bumetanide) or anion exchanger (SITS) was abolished by H2S donor NaHS, which attested to an important role of these transporters and chlorine conductivity of the membrane in the maintenance of the homeostasis of blood cells.


Assuntos
Bumetanida/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Sulfeto de Hidrogênio/farmacologia , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Adulto , Feminino , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária , Masculino , Adulto Jovem
6.
ACS Appl Mater Interfaces ; 11(38): 34609-34620, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31448889

RESUMO

Antimicrobial peptides (AMPs) can target bacterial membranes and kill bacteria through membrane structural damage and cytoplasmic leakage. A group of surfactant-like cationic AMPs was developed from substitutions to selective amino acids in the general formula of G(IIKK)3I-NH2, (called G3, a de novo AMP), to explore the correlation between AMP hydrophobicity and bioactivity. A threshold surface pressure over 12 mN/m was required to cause measurable antimicrobial activity and this corresponded to a critical AMP concentration. Greater surface activity exhibited stronger antimicrobial activity but had the drawback of worsening hemolytic activity. Small unilamellar vesicles (SUVs) with specific lipid compositions were used to model bacterial and host mammalian cell membranes by mimicking the main structural determinants of the charge and composition. Leakage from the SUVs of encapsulated carboxyfluorescein measured by fluorescence spectroscopy indicated a negative correlation between hydrophobicity and model membrane selectivity, consistent with measurements of the zeta potential that demonstrated the extent of AMP binding onto model SUV lipid bilayers. Experiments with model lipid membranes thus explained the trend of minimum inhibitory concentrations and selectivity measured from real cell systems and demonstrated the dominant influence of hydrophobicity. This work provides useful guidance for the improvement of the potency of AMPs via structural design, whilst taking due consideration of cytotoxicity.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Bactérias/crescimento & desenvolvimento , Membrana Eritrocítica/metabolismo , Teste de Materiais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Hemólise/efeitos dos fármacos , Humanos , Bicamadas Lipídicas/química
7.
Biochim Biophys Acta Proteins Proteom ; 1867(11): 140267, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31470132

RESUMO

Spectrin, the major protein component of the erythrocyte membrane skeleton has chaperone like activity and is known to bind membrane phospholipids and hemoglobin. We have probed the chaperone activity of spectrin in presence of hemoglobin and phospholipid SUVs of different compositions to elucidate the effect of phospholipid/hemoglobin binding on chaperone function. It is seen that spectrin displays a preference for hemoglobin over other substrates leading to a decrease in chaperone activity in presence of hemoglobin. A competition is seen to exist between phospholipid binding and chaperone function of spectrin, in a dose dependent manner with the greatest extent of decrease being seen in case of phospholipid vesicles containing aminophospholipids e.g. PS and PE which may have implications in diseases like hereditary spherocytosis where mutation in spectrin is implicated in its detachment from cell membrane. To gain a clearer understanding of the chaperone like activity of spectrin under in-vivo like conditions we have investigated the effect of macromolecular crowders as well as phosphorylation and glycation states on chaperone activity. It is seen that the presence of non-specific, protein and non-protein macromolecular crowders do not appreciably affect chaperone function. Phosphorylation also does not affect the chaperone function unlike glycation which progressively diminishes chaperone activity. We propose a model where chaperone clients adsorb onto spectrin's surface and processes that bind to and occlude these surfaces decrease chaperone activity.


Assuntos
Membrana Eritrocítica/química , Hemoglobinas/química , Chaperonas Moleculares/química , Espectrina/química , Animais , Bovinos , Membrana Eritrocítica/metabolismo , Hemoglobinas/metabolismo , Chaperonas Moleculares/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Ovinos , Espectrina/metabolismo
8.
Asian Pac J Cancer Prev ; 20(7): 2167-2176, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350981

RESUMO

Background: Smokeless tobacco (SLT) acts as a modifier of erythrocyte and platelet membranes by disrupting antioxidant system with the concomitant increase in free radical production and induction of apoptosis. Methods: The SLT users was that individuals used gutkha and khaini products (Khaleja/mahak chaini brand respectively) habitually, at least >20 times per week consists of 50-60 g during the last 2-4 years. Results: The gutkha and khaini users found to be significantly increased levels of iNOS (Inducible nitric oxide synthase) enzyme in plasma, erythrocytes, and platelet membranes when compared to normal controls. The gutkha and khaini users exhibited that the significant increase in the levels of gene expression of apoptotic proteins (Bcl2-B cell lymphoma gene 2, Bax, caspases 8, caspase 10, and caspase 12), IL-6 (Interleukin-6), and decreased levels of TNF-α (Tumor necrosis factor-alpha) and decreased expression of caspase 12 of khaini users were observed from blood samples. The significant increase in the concentrations of peroxynitrites (ONOO-), nitric oxide (NO) (Nitrates and nitrites), malondialdehyde (MDA), cholesterol, and phospholipids were reported in the smokeless tobacco users of erythrocytes and platelets. The experimental subjects showed that the increased osmotic fragility and decreased membrane fluidity of erythrocytes and platelets in comparison with non-tobacco users. The normal subjects had been exposed that the proper functioning of antioxidant enzymes and decreased enzyme activities of antioxidants were reported by SLT users. Conclusion: The smokeless tobacco products are exerted chronic damage to membranes of erythrocytes and platelets and elevation of apoptosis in the prolonged periods of human male volunteers.


Assuntos
Biomarcadores/metabolismo , Plaquetas/patologia , Eritrócitos/patologia , Uso de Tabaco/epidemiologia , Tabaco sem Fumaça/efeitos adversos , Adulto , Apoptose , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Estudos de Casos e Controles , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/patologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Seguimentos , Perfilação da Expressão Gênica , Humanos , Índia/epidemiologia , Masculino , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Prognóstico , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
Eur Biophys J ; 48(6): 503-511, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222413

RESUMO

A number of viruses causing sexually transmissible diseases are transmitted via mammalian seminal plasma. Several components of seminal plasma have been shown to influence those viruses and their physiological impact. To unravel whether components of seminal plasma could affect viruses transmitted via other pathways, it was investigated here whether the bovine seminal plasma protein PDC-109, belonging to the Fn-type 2 protein family, influences the activity of influenza A viruses, used as a model for enveloped viruses. We found that PDC-109 inhibits the fusion of influenza virus with human erythrocyte membranes and leads to a decreased viral infection in MDCK cells. In the presence of the head group of the phospholipid phosphatidylcholine, phosphorylcholine, the inhibitory effect of PDC-109 was attenuated. This indicates that the impact of the protein is mainly caused by its binding to viral and to erythrocyte membranes thereby interfering with virus-cell binding. Our study underlines that Fn-type 2 proteins have to be considered as new antiviral components present in mammalian seminal plasma.


Assuntos
Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Proteínas Secretadas pela Vesícula Seminal/farmacologia , Animais , Bovinos , Cães , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Hemaglutininas Virais/química , Vírus da Influenza A Subtipo H3N2/fisiologia , Células Madin Darby de Rim Canino , Fosforilcolina/farmacologia , Conformação Proteica/efeitos dos fármacos , Proteínas Secretadas pela Vesícula Seminal/metabolismo , Internalização do Vírus/efeitos dos fármacos
10.
Bull Exp Biol Med ; 167(2): 198-200, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236879

RESUMO

The effects of helium cold plasma on some parameters of metabolism of rat erythrocytes were studied after a course exposure (10 daily procedures, 1 min each). The intensity of free-radical processes in erythrocyte membranes, malondialdehyde concentration, and aldehyde dehydrogenase activity were analyzed. The exposure to helium cold plasma led to a significant increase in malondialdehyde level mostly associated with inhibition of its utilization. These changes were not related to activation of malondialdehyde synthesis in LPO reactions.


Assuntos
Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Malondialdeído/metabolismo , Gases em Plasma/farmacologia , Aldeído Desidrogenase/metabolismo , Animais , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Hélio , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar
11.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195708

RESUMO

Diets of dairy cows are often based on maize silage (MS), delivering lower amounts of n-3 fatty acids (FA) compared to grass silage-based diets. The fatty acid composition of the cell membrane can affect the cell function. We evaluated the effects of an MS-based diet on bovine red blood cell (RBC) membrane FA composition and dietary effects on controlled ATP release of RBC. In trial 1, German Holstein cows were fed an MS-based total mixed ration for 24 weeks. The FA composition of RBC membranes from repeatedly taken blood samples was analysed in addition to the abundance of the RBC membrane protein flotillin-1, which is involved in, for example, cell signalling. In trial 2, four rumen fistulated MS-fed cows were abomasally infused in a 4 × 4 Latin square model with three successively increasing lipid dosages (coconut oil, linseed-safflower oil mix (EFA; rich in n-3 FA), Lutalin®, providing conjugated linoleic acids (CLA) or the combination of the supplements, EFA + CLA) for six weeks, followed by a three-week washout period. In trial 2, we analysed RBC ATP release, flotillin-1, and the membrane protein abundance of pannexin-1, which is involved in ATP release as the last part of a signalling cascade. In trial 1, the total amount of n-3 FA in RBC membranes decreased and the flotillin-1 abundance increased over time. In trial 2, the RBC n-3 FA amount was higher after the six-week infusion period of EFA or EFA + CLA. Furthermore, depending on the dosage of FA, the ATP release from RBC increased. The abundance of flotillin-1 and pannexin-1 was not affected in trial 2. It is concluded that changes of the membrane FA composition influence the RBC function, leading to altered ATP release from intact bovine RBC.


Assuntos
Trifosfato de Adenosina/metabolismo , Indústria de Laticínios , Dieta , Membrana Eritrocítica/metabolismo , Ácidos Graxos/farmacologia , Animais , Bovinos , Conexinas/metabolismo , Suplementos Nutricionais , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Proteínas de Membrana/metabolismo
12.
Int J Lab Hematol ; 41 Suppl 1: 95-101, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31069991

RESUMO

Hereditary hemolytic anemia (HHA) is a group of genetically and phenotypically heterogeneous disorders characterized by premature destruction of red blood cells (RBCs) with clinical manifestations ranging from asymptomatic to marked hemolytic anemia. There are three main categories of HHA: (a) RBC membrane defects; (b) hemoglobinopathies/thalassemias; and (c) RBC enzyme deficiencies. Hyperbilirubinemia is a frequent consequence of hemolytic anemia and can lead to bilirubin-associated neurotoxicity in neonates and to jaundice, and formation of gall stones in adults. Hyperbilirubinemia can also be caused by impaired bilirubin conjugation due to polymorphisms and mutations in genes involved in bilirubin metabolism (eg, UGT1A1). Neonates with HHA and co-inherited variants impairing bilirubin conjugation are at increased risk of bilirubin-associated toxicity. Prior to the advent of next-generation sequencing (NGS), molecular diagnosis of these disorders was limited to targeted single gene Sanger sequencing. However, NGS is making its way into the standard diagnostic workup of complex and multigene disorders like HHA. This review will focus on the molecular updates of HHA with particular focus on the neonatal and pediatric population.


Assuntos
Anemia Hemolítica Congênita , Hiperbilirrubinemia Neonatal , Adulto , Anemia Hemolítica Congênita/sangue , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/genética , Membrana Eritrocítica/genética , Membrana Eritrocítica/metabolismo , Feminino , Cálculos Biliares/sangue , Cálculos Biliares/diagnóstico , Cálculos Biliares/genética , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/genética , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/genética , Recém-Nascido , Masculino , Mutação , Patologia Molecular
13.
PLoS Pathog ; 15(5): e1007761, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31071194

RESUMO

Plasmodium falciparum mediates adhesion of infected red blood cells (RBCs) to blood vessel walls by assembling a multi-protein complex at the RBC surface. This virulence-mediating structure, called the knob, acts as a scaffold for the presentation of the major virulence antigen, P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1). In this work we developed correlative STochastic Optical Reconstruction Microscopy-Scanning Electron Microscopy (STORM-SEM) to spatially and temporally map the delivery of the knob-associated histidine-rich protein (KAHRP) and PfEMP1 to the RBC membrane skeleton. We show that KAHRP is delivered as individual modules that assemble in situ, giving a ring-shaped fluorescence profile around a dimpled disk that can be visualized by SEM. Electron tomography of negatively-stained membranes reveals a previously observed spiral scaffold underpinning the assembled knobs. Truncation of the C-terminal region of KAHRP leads to loss of the ring structures, disruption of the raised disks and aberrant formation of the spiral scaffold, pointing to a critical role for KAHRP in assembling the physical knob structure. We show that host cell actin remodeling plays an important role in assembly of the virulence complex, with cytochalasin D blocking knob assembly. Additionally, PfEMP1 appears to be delivered to the RBC membrane, then inserted laterally into knob structures.


Assuntos
Membrana Eritrocítica/parasitologia , Eritrócitos/parasitologia , Malária Falciparum/parasitologia , Peptídeos/metabolismo , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/metabolismo , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Humanos , Malária Falciparum/metabolismo , Microscopia Eletrônica de Varredura , Peptídeos/química , Proteínas de Protozoários/química , Virulência
14.
Biomed Pharmacother ; 116: 108925, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112874

RESUMO

BACKGROUND: Chronic hyperglycaemia-induced haematological changes increase the risk of cardiovascular complications in diabetic patients. The administration of insulin injection as a bolus is accompanied with increased blood viscosity, which is not recommended for patients with congestive heart failure. Momordica balsamina methanolic extract (MB) has previously been shown to possess anti-hyperglycaemic and renal dysfunction ameliorative effects; however, the haematological effects of MB have not been shown. The current study therefore, investigated the short-term effects MB on selected haematological parameters in streptozotocin (STZ)-induced diabetic rats. METHODS: Briefly, the air-dried Momordica balsamina leaves were sequentially extracted with methanol to yield a methanolic extract. STZ-induced diabetic rats were divided into untreated and treated groups with insulin (170 µg kg-1 s.c.) and metformin (500 mg kg-1 p.o.) MB (250 mg kg-1 p.o.). MB was administered twice daily for the 5-week experimental period. Blood glucose concentration was monitored weekly. Animals were sacrificed terminally. Blood and kidneys were collected for haematological and biochemical analysis respectively. RESULTS: Treatment with MB significantly decreased blood glucose concentration and improved erythropoietin secretion, thus significantly increasing red blood cell production in treated diabetic animals by comparison to untreated animals. MB also significantly improved haemoglobin concentrations and moderately increased erythrocyte indices specifically, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) and mean corpuscular haemoglobin (MCH) to no significance by comparison to untreated diabetic animals. MB treatment decreased the oxidative stress evoked by the induction of diabetes while improving the antioxidant status of treated animals by comparison to untreated animals respectively. CONCLUSIONS: Administration of Momordica balsamina methanolic extract protects against some injurious haematological changes induced by hyperglycaemia, which may reduce the risks of cardiovascular complications.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Metanol/química , Momordica/química , Extratos Vegetais/uso terapêutico , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Membrana Eritrocítica/metabolismo , Eritropoetina/sangue , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/metabolismo
15.
PLoS One ; 14(5): e0216467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31083675

RESUMO

Abnormal red blood cell (RBC) adhesion to endothelial αvß3 plays a crucial role in triggering vaso-occlusive episodes in sickle cell disease (SCD). It is known that epinephrine, a ß-adrenergic receptor (ß-AR) stimulator, increases the RBC surface density of active intercellular adhesion molecule-4 (ICAM-4) which binds to the endothelial αvß3. It has also been demonstrated that in human embryonic kidney 293 cells, mouse cardiomyocytes, and COS-7 cell lines, the ß-adrenergic and renin-angiotensin systems are interrelated and that there is a direct interaction and cross-regulation between ß-AR and angiotensin II type 1 receptor (AT1R). Selective blockade of AT1R reciprocally inhibits the downstream signaling of ß-ARs, similar to the inhibition observed in the presence of a ß-AR-blocker. However, it is not known if this mechanism is active in human RBCs. Here, we studied the effect of valsartan, an AT1R blocker, on the surface density of active ICAM-4 receptors in normal, sickle cell trait, and homozygous sickle RBCs. We applied single molecule force spectroscopy to detect active ICAM-4 receptors on the RBC plasma membrane with and without the presence of valsartan and epinephrine. We found that epinephrine significantly increased whereas valsartan decreased their surface density. Importantly, we found that pretreatment of RBCs with valsartan significantly impeded the activation of ICAM-4 receptors induced by epinephrine. The observed reduced expression of active ICAM-4 receptors on the RBC plasma membrane leads us to conjecture that valsartan may be used as a supporting remedy for the prevention and treatment of vaso-occlusive crisis in SCD.


Assuntos
Moléculas de Adesão Celular/metabolismo , Epinefrina/farmacologia , Membrana Eritrocítica/metabolismo , Eritrócitos Anormais/metabolismo , Traço Falciforme/metabolismo , Valsartana/farmacologia , Adolescente , Adulto , Animais , Células COS , Chlorocebus aethiops , Membrana Eritrocítica/ultraestrutura , Eritrócitos Anormais/ultraestrutura , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Microscopia de Força Atômica , Receptor Tipo 1 de Angiotensina/metabolismo , Traço Falciforme/patologia
16.
Oxid Med Cell Longev ; 2019: 5172480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089408

RESUMO

Baoyuan decoction (BYD), a traditional representative formula, has a long usage history in the treatment of cardiovascular diseases. Since the hyperlipidemia-induced dysfunction of erythrocyte is one of the most important causes of cardiovascular diseases, the improving effects of BYD against high-fat diet (HFD) induced the physiological and physical function of the erythrocytic injury and the potential mechanisms were deeply researched in this study. After 6 weeks of drug treatment, all doses of BYD had significantly decreased the lipid peroxidation in plasma of HFD-induced ApoE-/- mice, even if it had not improved the lipid levels. Then, the erythrocyte-related experimental results showed that BYD had reduced erythrocyte osmotic fragility, stabilized erythrocyte membrane skeleton protein 4.2, and reformed the erythrocyte morphological changes by decreasing erythrocyte membrane lipid peroxidation levels. This study demonstrated that BYD may ameliorate the physiological and physical function of erythrocyte in hyperlipidemic mice through the antioxidant effect on erythrocyte membranes.


Assuntos
Antioxidantes/farmacologia , Apolipoproteínas E/deficiência , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologia , Eritrócitos/patologia , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Animais , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Eritrócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Fragilidade Osmótica , Oxirredução
17.
Chemosphere ; 229: 103-111, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31078025

RESUMO

Triclosan (TCS) is a broad-spectrum antimicrobial used in personal care products, household items, and medical devices. Owing to its apoptotic potential against tumor cells, TCS has been proposed for the treatment of malignancy. A major complication of chemotherapy is anemia, which may result from direct erythrocyte hemolysis or premature cell death known as eryptosis. Similar to nucleated cells, eryptotic cells lose membrane asymmetry and Ca2+ regulation, and undergo oxidative stress, shrinkage, and activation of a host of kinases. In this report, we sought to examine the hemolytic and eryptotic potential of TCS and dissect the underlying mechanistic scenarios involved there in. Hemolysis was spectrophotometrically evaluated by the degree of hemoglobin release into the medium. Flow cytometry was utilized to detect phosphatidylserine (PS) exposure by annexin-V binding, intracellular Ca2+ by Fluo-3/AM fluorescence, and oxidative stress by 2-,7-dichlorodihydrofluorescin diacetate (DCFH2-DA). Incubation of cells with 10-100 µM TCS for 1-4 h induced time- and dose-dependent hemolysis. Moreover, TCS significantly increased the percentage of eryptotic cells as evident by PS exposure (significantly enhanced annexin-V binding). Interestingly, TCS-induced eryptosis was preceded by elevated intracellular Ca2+ levels but was not associated with oxidative stress. Cotreatment of erythrocytes with 50 µM TCS and 50 µM SB203580 (p38 MAPK inhibitor), or 300 µM necrostatin-1 (receptor-interacting protein 1 (RIP1) inhibitor) significantly ameliorated TCS-induced PS externalization. We conclude that TCS is cytotoxic to erythrocytes by inducing hemolysis and stimulating premature death at least in part through Ca2+ mobilization, and p38 MAPK and RIP1 activation.


Assuntos
Cálcio/metabolismo , Poluentes Ambientais/toxicidade , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Triclosan/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Eriptose/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilserinas , Espécies Reativas de Oxigênio/metabolismo
18.
Blood Cells Mol Dis ; 77: 61-66, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30974390

RESUMO

Glucose transporter 1 (GLUT1) is one of 13 members of the human equilibrative glucose transport protein family and the only glucose transporter thought to be expressed in human erythrocyte membranes. Although GLUT1 has been shown to be anchored to adducin at the junctional spectrin-actin complex of the membrane through interactions with multiple proteins, whether other populations of GLUT1 also exist in the human erythrocyte membrane has not been examined. Because GLUT1 plays such a critical role in erythrocyte biology and since it comprises 10% of the total membrane protein, we undertook to evaluate the subpopulations of erythrocyte GLUT1 using single particle tracking. By monitoring the diffusion of individual AlexaFluor 488-labeled GLUT1 molecules on the surfaces of intact erythrocytes, we are able to identify three distinct subpopulations of GLUT1. While the mobility of the major subpopulation is similar to that of the anion transporter, band 3, both a more mobile and more anchored subpopulation also exist. From these studies, we conclude that ~65% of GLUT1 resides in similar or perhaps the same protein complex as band 3, while the remaining 1/3rd are either freely diffusing or interacting with other cytoskeletally anchored membrane protein complexes.


Assuntos
Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Biomarcadores , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Microscopia de Fluorescência , Imagem Molecular , Transporte Proteico , Coloração e Rotulagem
19.
J Therm Biol ; 81: 98-102, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30975429

RESUMO

Measuring the impedance of heated suspensions of erythrocytes and erythrocyte ghost membranes, two thermally-induced alterations are registered in the plasma membrane at TA (denaturation of spectrin with inducing temperature at 49,5 °C) and TG (hyperthermic activation of basal ion permeability with inducing temperature at 60.7 °C). In this study erythrocytes from 9 healthy patients and 15 patients with hemolytic anemia were studied and divided into four groups depending on their TA and TG top temperatures. The TA and TG of erythrocytes with hemoglobinopathy were the same as those of control erythrocytes while those of erythrocytes with membranopathy were significantly reduced. In erythrocytes with severe membranopathy, the TG was decreased by about 5 °C. In latter cells the normal value of TG was restored and the resistance to thermal haemolysis was increased by 90% after the specific stabilization of band 3 protein by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS). Obtained results indicate the involvement of band 3 in the membrane alteration at TG and in the heat target responsible for thermal haemolysis.


Assuntos
Anemia Hemolítica/metabolismo , Anemia Hemolítica/patologia , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/patologia , Hemólise , Temperatura Alta , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Humanos , Espectrina/metabolismo
20.
PLoS One ; 14(4): e0215447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002688

RESUMO

An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) transformation of a RBC. The coarse-grained (CG)-RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.


Assuntos
Algoritmos , Deformação Eritrocítica , Membrana Eritrocítica/metabolismo , Eritrócitos Anormais/metabolismo , Eritrócitos/metabolismo , Modelos Biológicos , Fenômenos Biomecânicos , Tamanho Celular , Membrana Eritrocítica/ultraestrutura , Eritrócitos/ultraestrutura , Eritrócitos Anormais/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura
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