Extracellular H2O2, peroxiredoxin, and glutathione reductase alter Neospora caninum invasion and proliferation in Vero cells.

Neospora caninum is a protozoan member of the Apicomplexa phylum and is closely connected with abortion in cattle. The development of the parasite in host cells is characterized by the active secretion of proteins, allied to the tight control of the redox status. In this sense, elucidating the mechanisms related to the role of the redox agents and enzymes during the invasion and proliferation of N. caninum may contribute to developing novel forms of neosporosis control. In this study we verified the effects of the recombinant forms of N. caninum glutathione reductase (rNcGR) and thioredoxin-dependent peroxide reductase (rNcPrx), as well as H2O2 in the tachyzoite invasion and proliferation. rNcPrx interfered in the N. caninum invasion in a redox state manner. Oxidized rNcPrx inhibited the N. caninum invasion and proliferation with no toxic effects observed in Vero cells. In contrast, lower concentrations of H2O2 (10 µM) stimulated the N. caninum invasion, which was reverted in higher doses (>100 µM). H2O2 inhibited the parasite proliferation in lower concentrations than cytotoxicity in host cells, resulting in a positive selectivity index (1.8). Besides, rNcPrx (reduced and non-reduced) and rNcGR inhibited the parasite proliferation without affecting the host cell. Our results indicate the connection between the N. caninum development and the redox state, contributing to the elucidation of parasite propagation and control mechanisms.

Genetic Variations on Redox Control in Cardiometabolic Diseases: The Role of Nrf2.

The transcription factor Nrf2 is a master regulator of multiple cytoprotective genes that maintain redox homeostasis and exert anti-inflammatory functions. The Nrf2-Keap1 signaling pathway is a paramount target of many cardioprotective strategies, because redox homeostasis is essential in cardiovascular health. Nrf2 gene variations, including single nucleotide polymorphisms (SNPs), are correlated with cardiometabolic diseases and drug responses. SNPs of Nrf2, KEAP1, and other related genes can impair the transcriptional activation or the activity of the resulting protein, exerting differential susceptibility to cardiometabolic disease progression and prevalence. Further understanding of the implications of Nrf2 polymorphisms on basic cellular processes involved in cardiometabolic diseases progression and prevalence will be helpful to establish more accurate protective strategies. This review provides insight into the association between the polymorphisms of Nrf2-related genes with cardiometabolic diseases. We also briefly describe that SNPs of Nrf2-related genes are potential modifiers of the pharmacokinetics that contribute to the inter-individual variability.

Hyperbaric oxygenation improves redox control and reduces mortality in the acute phase of myocardial infarction in a rat model.

Among the mechanisms of action of hyperbaric oxygenation (HBO), the chance of reducing injury by interfering with the mechanisms of redox homeostasis in the heart leads to the possibility of extending the period of viability of the myocardium at risk. This would benefit late interventions for reperfusion to the ischemic area. The objective of the present study was to investigate the changes in the redox system associated with HBO therapy maintained during the first hour after coronary occlusion in an acute myocardial infarction (MI) rat model. Surviving male rats (n=105) were randomly assigned to one of three groups: Sham (SH=26), myocardial infarction (MI=45) and infarction+hyperbaric therapy (HBO=34, 1 h at 2.5 atm). After 90 min of coronary occlusion, a sample of the heart was collected for western blot analysis of total protein levels of superoxide dismutase, catalase, peroxiredoxin and 3­nitrotyrosine. Glutathione was measured by enzyme­linked immunosorbent assay (ELISA). The detection of the superoxide radical anion was carried out by oxidation of dihydroethidium analyzed with confocal microscopy. The mortality rate of the MI group was significantly higher than that of the HBO group. No difference was noted in the myocardial infarction size. The oxidized/reduced glutathione ratio and peroxiredoxin were significantly higher in the SH and MI when compared to the HBO group. Superoxide dismutase enzymes and catalase were significantly higher in the HBO group compared to the MI and SH groups. 3­Nitrotyrosine and the superoxide radical were significantly lower in the HBO group compared to these in the MI and SH groups. These data demonstrated that hyperbaric oxygenation therapy decreased mortality by improving redox control in the hearts of rats in the acute phase of myocardial infarction.

Especies reactivas del oxígeno: formación, funcion y estrés oxidativo / Reactive oxygen species: training, function and oxidative stress

Resumen Las especies reactivas del oxígeno (ROS) son producidas como una consecuencia del metabolismo aeróbico fisiológico normal. La cadena de transporte de electrones de la mitocondria, los peroxisomas, la NADPH oxidasa, la óxido nítrico sintetasa desacoplada y el sistema del citocromo P450 son las fuentes más importantes de producción de los ROS. El desbalance entre la producción de los ROS y el sistema de defensa antioxidante en los sistemas vivos ocasiona una ruptura de la función celular y daño. Este desbalance ocurre por una sobreproducción de ROS y una reducción del mecanismo de defensa antioxidante. Las acciones protectoras contra los ROS son llevadas a cabo por varias enzimas (superóxido dismutasa, catalasa y glutatión peroxidasa) y también por compuestos no enzimáticos (vitamina E, ascorbato, glutatión, transferrina, ceruloplasmina, etc.). Los ROS son moduladores cruciales de las funciones celulares. A bajas concentraciones, los ROS son participantes esenciales en la señalización celular, la inducción de la respuesta mitogénica, la defensa contra agentes infecciosos, mientras que el exceso de los ROS puede alterar la función celular normal y promover el daño irreversible a lípidos, ácidos nucleicos y a proteínas celulares. Los ROS, especialmente el H2O2, sirven como moléculas mensajeras por medio de la modificación oxidativa de proteínas de señalización. Entonces, un balance entre la producción de los ROS y su remoción permite una función celular normal, mientras que un desequilibrio causa estrés oxidativo con consecuencias patológicas.

Abstract Reactive oxigen species (ROS) are produced as the consequence of the normal aerobic physiological metabolism. The electron transport chain in mitochondrial, peroxisomes, NADPH oxidases, uncoupled nitric oxide synthase (NOS) and cytochrome P450 system are the most important sources of ROS production. The imbalance of the ROS production and antioxidants defense system in the living systems causes oxidative stress brings to cellular function disruption and damage. This imbalance occurs due to over production of ROS and reduction of the antioxidant defense mechanism. Protective actions against ROS are performed by several enzymes (superoxide dismutase, catalase and glutation peroxidase) as well as nonenzimatic compounds (vitamin E, ascorbate, glutathione, transferrin, ceruloplasmin, etc). ROS are crucial modulators of cellular functions. At low concentrations, ROS are essential participants in cell signaling, induction of mitogenic response, involvement in defense against infectious agents, whereas excess ROS can disrupt normal cellular function and promote irreversible damage to cellular lipids, nucleic acids, and proteins. ROS, especially H2O2, serve as a signal molecule through oxidative modification of signaling proteins. Thus, a balance between ROS production and their removal allows for normal cellular function, whereas an imbalance causes oxidative stress with pathological consequences.