The reaction of ascorbic acid with different heme iron redox states of myoglobin Antioxidant and prooxidant aspects

AbstractThe interaction of ascorbate with different heme iron redox states of myoglobin (ferrylmyoglobin, FeIV=O; metmyoglobin, FeIII; and oxymyoglobin FeIIO2) was examined by e.s.r. and absorption spectroseopy. The reaction of ascorbate with ferryl- or met-myoglobin resulted in ascorbyl radical production. The interaction of ascorbate with oxymyoglobin proceeded with formation of ascorbyl radical, hydrogen peroxide, and an overall oxidation of oxymyoglobin to metmyoglobin. The latter reaction proceeded via an oxoferryl complex intermediate - corresponding to ferrylmyoglobin and identified by treatment of the reaction mixture with Na2S. These observations are consistent with a concerted electron transfer mechanism, whereby the two electrons required for the reduction of oxygen to hydrogen peroxide are donated by ascorbic acid and the heme iron. The antioxidant and prooxidant aspects of these redox transitions are discussed in terms of their kinetic properties

Redox interactions of nitric oxide with dopamine and its derivatives

Nitric oxide (NO) is a ubiquitous diffusible messenger in the central nervous system. NO and derived nitrogen species may interact with catecholamines, thus, modifying not only its regulatory actions but also producing oxidants and free radicals that are likely to trigger toxic pathways in the nervous system. Oxidative pathways and chain oxidation reactions triggered by catecholamines may be broken by ascorbate and glutathione, of which there is ample supply in the brain. At the subcellular level, mitochondria and cytosolic dopamine storage vesicles are likely to provide site-specific settings for NO and catecholamines interactions. Thus, a complex picture emerges in which the steady- state levels of the individual reactants, the rate constants of the reactions involved, the oxygen tension, and the compartmentalization of reactions determine the biological significance of the redox interactions between NO and dopamine metabolism in the brain. The physiological relevance of NO-driven chemical modifications of dopamine and its derivatives and the ensuing free radical production are discussed in connection with the neurodegeneration inherent in Parkinson's disease.http://www.sciencedirect.com/science/article/B6TCN-4F5S809-2/1/71b1057aac4a62ea0c5684eb2d42f11

Mitochondrial damage by nitric oxide is potentiated by dopamine in PC12 cells

AbstractMitochondrial damage in PC12 cells, a model for dopaminergic cells, was examined in terms of the contribution of oxidative stress, nitric oxide (NO), and dopamine to impairment of mitochondrial respiratory control (RC). A kinetic analysis suggested that the oxidative deamination of dopamine catalyzed by monoamine oxidase (MAO) was not a significant source of hydrogen peroxide, because of constrains imposed by the low cytosolic level of dopamine. NO induced irreversible damage of mitochondrial complex I in PC12 cells: this damage followed a sigmoid response on NO concentration with a well-defined threshold level. Dopamine did not elicit damage of mitochondria in PC12 cells; however, the amine potentiated the effects of NO at or near the threshold level, thus leading to irreversible impairment of mitochondrial respiration. This synergism between NO and dopamine was not observed at NO concentrations below the threshold level. Depletion of dopamine from the storage vesicles by reserpine protected mitochondria from NO damage. Dopamine oxidation by NO increased with pH, and occurred at modest levels at pH 5.5. In spite of this, calculations showed that the oxidation of dopamine in the storage vesicles (pH 5.5) was higher than that in the cytosol (pH 7.4), due to the higher dopamine concentration in the storage vesicles (millimolar range) compared to that in the cytosol (micromolar range). It is suggested that storage vesicles may be the cellular sites where the potential for dopamine oxidation by NO is higher.These data provide further support to the hypothesis that dopamine renders dopaminergic cells more susceptible to the mitochondrial damaging effects of NO. In the early stages of Parkinson's disease, NO production increases until reaching a point near the threshold level that induces neuronal damage. Dopamine stored in dopaminergic cells may cause these cells to be more susceptible to the deleterious effects of NO, which involve irreversible impairment of mitochondrial respiration

Características antropométricas y nivel de condición física en relación con el estado ponderal en niños chilenos de edad preescolar

The purpose of this study was to describe anthropometric and physical fitness characteristics of low-income Chilean preschool children and to examine whether weight status influences children’s performance on fitness tests. A total of 434 preschool children (246 boys; 5.48 ± 0.31 years) participated in our study. Anthropometry (weight, height, body mass index -BMI- and waist circumference) and fitness tests (handgrip strength test, standing long jump and 20 m sprint) were assessed by trained nutritionists and physical education teachers, respectively. Significant differences in anthropometry and fitness tests between boys and girls were found. The prevalence of overweight was higher in girls; in contrast to that of obesity. Compared to normal-weight children, overweight/obese boys and girls were heavier and had greater waist circumference (P < 0.001), were taller (P ≤ 0.002), and showed higher performance in handgrip strength (P ≤ 0.027) but not in standing long jump nor 20 m sprint (P ≥ 0.052). Screening physical fitness levels in overweight/obese preschool children could be an important tool in order to design an efficacy physical activity programme.El objetivo de este estudio fue describir las características antropométricas y el nivel de condición física de preescolares chilenos de bajo nivel socioeconómico y examinar si el estado ponderal influye en el rendimiento de los niños en las pruebas de condición física. Un total de 434 preescolares (246 niños; 5,48 ± 0,31 años) participaron en nuestro estudio. Antropometría (peso, talla, índice de masa corporal –IMC– y perímetro de cintura) y tests de condición física (test de fuerza de prensión manual, test de salto de longitud y 20 m sprint) fueron evaluados por nutricionistas entrenados y profesores de educación física, respectivamente. Se encontraron diferencias significativas en antropometría y tests de condición física entre niños y niñas. La prevalencia de sobrepeso fue mayor en las niñas; en contraste con la de la obesidad. En comparación con los preescolares con normopeso, los niños y niñas con sobrepeso/obesidad pesaron más y tuvieron mayor perímetro de cintura (P < 0.001), eran más altos (P ≤ 0.002) y mostraron mayor rendimiento en el test de fuerza de prensión manual (P ≤ 0.027), pero no en el test de salto de longitud ni en el test de sprint de 20 m (P ≥ 0.052). Detectar los niveles de condición física en preescolares con sobrepeso/obesidad puede ser una herramienta importante para diseñar programas eficaces de actividad física.They would like to thank the “Corporación Municipal de Educación y Salud” of Ñuñoa for funding the study. Likewise, we thank Francisco B. Ortega from the University of Granada, Spain, for his valuable comments on an earlier draft. Cristina Cadenas-Sánchez is supported by a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-068829)

Spatial Variations in Vitreous Oxygen Consumption

We investigated the spatial variation of vitreous oxygen consumption in enucleated porcine eyes. A custom made oxygen source was fabricated that could be localized to either the mid or posterior vitreous cavity and steady state vitreous oxygen tension was measured as a function of distance from the source using a commercially available probe. The reaction rate constant of ascorbate oxidation was estimated ex vivo by measuring the change in oxygen tension over time using vitreous harvested from porcine eyes. Vitreous ascorbate from mid and posterior vitreous was measured spectrophotometrically. When the oxygen source was placed in either the mid-vitreous (N = 6) or the posterior vitreous (N = 6), we measured a statistically significant decrease in vitreous oxygen tension as a function of distance from the oxygen source when compared to control experiments without an oxygen source; (p<0.005 for mid-vitreous and p<0.018 for posterior vitreous at all distances). The mid-vitreous oxygen tension change was significantly different from the posterior vitreous oxygen tension change at 2 and 3mm distances from the respective oxygen source (p<0.001). We also found a statistically significant lower concentration of ascorbate in the mid-vitreous as compared to posterior vitreous (p = 0.02). We determined the reaction rate constant, k = 1.61 M^(-1)s^(-1) ± 0.708 M^(-1)s^(-1) (SE), of the oxidation of ascorbate which was modeled following a second order rate equation. Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid-vitreous. We also show spatial variations in vitreous ascorbate concentration