RESUMO
We collected peripheral blood from thirty-nine elite male endurance runners at rest (24 hours after the last exercise session) and used the Allergy Questionnaire for Athletes score and plasma specific IgE level to separate them into atopic and non-atopic athletes. Neutrophils obtained from atopic and non-atopic athletes were subsequently stimulated in vitro with fMLP (N-formyl-methionyl-leucyl-phenylalanine), LPS (lipopolysaccharide), or PMA (phorbol 12-myristate 13-acetate). Neutrophils from non-atopic runners responded appropriately to LPS, as evidenced by the production of pro (IL-8, TNF-α, and IL-6) and anti-inflammatory (IL-10) cytokines. Neutrophils from atopic elite runners exhibited lower responses to LPS stimulus as indicated by no increase in IL-1ß, TNF-α, and IL-6 production. Neutrophils from non-atopic and atopic runners responded similarly to fMLP stimulation, indicating that migration function remained unaltered. Both groups were unresponsive to PMA induced reactive oxygen species (ROS) production. Training hours and training volume were not associated with neutrophil IgE receptor gene expression or any evaluated neutrophil function. Since non-atopic runners normally responded to LPS stimulation, the reduced neutrophil response to the stimuli was most likely due to the atopic state and not exercise training. The findings reported are of clinical relevance because atopic runners exhibit a constant decline in competition performance and are more susceptible to invading microorganisms.
Assuntos
Hipersensibilidade Imediata/imunologia , Neutrófilos/imunologia , Adulto , Células Cultivadas , Citocinas/metabolismo , Suscetibilidade a Doenças , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/genética , Infecções , Lipopolissacarídeos/metabolismo , Masculino , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Ativação de Neutrófilo , Resistência Física , Corrida , Inquéritos e QuestionáriosRESUMO
We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.
Assuntos
Suplementos Nutricionais , Exercício Físico , Glutamina/farmacologia , Controle Glicêmico/estatística & dados numéricos , Joelho/fisiologia , Músculo Esquelético/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Brasil , Método Duplo-Cego , Feminino , Avaliação Geriátrica/métodos , Humanos , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , TorqueRESUMO
A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.
Assuntos
Antivirais/farmacologia , Glutamina/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Linhagem Celular Tumoral , Interações Hospedeiro-Patógeno , Humanos , Neoplasias/metabolismo , Neoplasias/virologia , Virulência/efeitos dos fármacos , Vírus/efeitos dos fármacos , Vírus/patogenicidadeRESUMO
A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.
RESUMO
Neutrophils were traditionally considered as short-lived cells with abundant secretory and protein synthetic activity. Recent studies, however, indicate neutrophils are in reality a heterogeneous population of cells. Neutrophils differentiate from pluripotent stem cells in the bone marrow, and can further mature in the blood stream and can have different phenotypes in health and disease conditions. Neutrophils undergo primary functions such as phagocytosis, production of reactive oxygen species (ROS), release of lipid mediators and inflammatory proteins (mainly cytokines), and apoptosis. Neutrophils stimulate other neutrophils and trigger a cascade of immune and inflammatory responses. The underpinning intracellular metabolisms that support these neutrophil functions are herein reported. It has been known for many decades that neutrophils utilize glucose as a primary fuel and produce lactate as an end product of glycolysis. Neutrophils metabolize glucose through glycolysis and the pentose- phosphate pathway (PPP). Mitochondrial glucose oxidation is very low. The PPP provides the reduced nicotinamide adenine dinucleotide phosphate (NADPH) for the NADPH-oxidase (NOX) complex activity to produce superoxide from oxygen. These cells also utilize glutamine and fatty acids to produce the required adenosine triphosphate (ATP) and precursors for the synthesis of molecules that trigger functional outcomes. Neutrophils obtained from rat intraperitoneal cavity and incubate for 1 hour at 37°C metabolize glutamine at higher rate than that of glucose. Glutamine delays neutrophil apoptosis and maintains optimal NOX activity for superoxide production. Under limited glucose provision, neutrophils move to fatty acid oxidation (FAO) to obtain the required energy for the cell function. FAO is mainly associated with neutrophil differentiation and maturation. Hypoxia, hormonal dysfunction, and physical exercise markedly change neutrophil metabolism. It is now become clear that neutrophil metabolism underlies the heterogeneity of neutrophil phenotypes and should be intense focus of investigation.
Assuntos
Glucose/metabolismo , Glutamina/metabolismo , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Animais , Hipóxia Celular/fisiologia , Citocinas/metabolismo , Ácidos Graxos/metabolismo , Hormônios/farmacologia , Humanos , Mitocôndrias/metabolismo , NADP/metabolismo , Neutrófilos/citologia , Neutrófilos/enzimologia , Neutrófilos/imunologia , Condicionamento Físico Animal/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
The present study aimed to compare the immune and inflammatory responses between atopic (n=20) and non-atopic (n=39) elite endurance athletes. Fifty-nine elite runners and triathletes were assessed for the following measurements: Th1, Th2 and lymphocyte phenotyping and plasma levels of cortisol, chemokines, inflammatory cytokines and specific immunoglobulin E (IgE). Levels of salivary IgA, allergic symptoms and training data were also evaluated. No difference was observed in baseline lymphocyte levels. However, the Th1 lymphocytes of atopic athletes presented a lower response after activation. In contrast to this result, levels of salivary IgA and CXCL9 chemokine were higher in the atopic athletes. It was observed that the volume of training per week was linearly associated with Th1 levels, allergic symptoms and IgE levels. In addition, linear multiple regression analysis demonstrated that the volume of training was the only factor associated with allergic symptoms in atopic athletes (r=0.53; p=0.04). These results suggest that compared to non-atopic athletes, atopic athletes present a reduced Th1 response and higher levels of salivary IgA. Training volume is associated with the immune response and allergic symptoms, which suggests that they may play a role in the atopy in elite endurance athletes.