1,721,001 research outputs found
Bioactivity of sesquiterpenes: compounds that protect from alcohol-induced gastric mucosal lesions and oxidative damage
Full text linkSesquiterpene lactones of the guaianolide and eudermanolide types are considered of interest because they have an effect in the regulation and prevention of oxidative damage and inflammation-mediated biological damage. Dehydroleucodine, a natural sesquiterpene isolated from Artemisia douglasiana Besser, and ilicic aldehyde, a semi-synthetic sesquiterpene lactones, showed in vivo protection in ethanol-induced gastric mucosa damage. This action was determined by in situ gastric mucosa chemiluminescence and by tissue antioxidant content.Fil: Repetto, Marisa G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Boveris, Alberto Antonio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Oxidative stress and mitochondrial damage in coronary artery bypass graft surgery: Effects of antioxidant treatments
Full text linkWe examined antioxidant actions in 73 patients undergoing coronary artery surgery by assessing mitochondrial damage and oxidative stress in ventricular biopsies obtained at preischemia and postreperfusion. Those patients who received antioxidant therapy benefited by less oxidative stress and mitochondrial damage.Fil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ferreira, Ricardo. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Grana, Daniel Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin
Brain mitochondrial dysfunction in aging
Full text linkAging of mammalian brain is associated with a continuous decrease of the capacity to produce ATP by oxidative phosphorylation. The impairment of mitochondrial function is mainly due to diminished electron transfer by complexes I and IV, whereas inner membrane H(+) impermeability and F(1)-ATP synthase activity are only slightly affected. Dysfunctional mitochondria in aged rodents show decreased rates of respiration and of electron transfer, decreased membrane potential, increased content of the oxidation products of phospholipids and proteins, and increased size and fragility. In aging mice, the activities of brain mitochondrial enzymes (complexes I and IV and mtNOS) are linearly correlated with neurological performance (tightrope and T-maze tests) and with median life span and negatively correlated with the mitochondrial content of lipid and protein oxidation products. Conditions that increased mice median life span, such as moderate exercise, vitamin E supplementation, caloric restriction, and high spontaneous neurological activity; also improved neurological performance and mitochondrial function in aged brain. The diffusion of mitochondrial NO and H(2)O(2) to the cytosol is decreased in the aged brain and may be a factor for reduced mitochondrial biogenesis.Fil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires; ArgentinaFil: Navarro, Ana. Universidad de Cádiz; Españ
The regulation of cell energetics and mitochondrial signaling by nitric oxide
No full textThe recognition that nitric oxide (NO) acts as a reversible inhibitor of cytochrome oxidase activity competitively with O 2 produced a Copernican revolution in the understanding of the regulation of respiration, especially at low tissue pO 2 . It is now understood that tissue O2 uptake depends on the O2 /NO ratio, a concept that has both experimental and mathematical support. Mitochondrial O2 production, stimulated by NO itself, prevents the inhibition of cytochrome oxidase by NO, providing the reversibility of the regulatory mechanism. The calculated intramitochondrial NO levels (100 – 360 nM) are in the range of concentrations, 80 – 200 nM NO, that inhibit by 50% cytochrome oxidase activity. Mitochondria have their own source of NO with mtNOS, a transcript of nNOS- α . This is an integral protein of the inner membrane and a voltage-dependent enzyme, and its activity inhibits mitochondrial O 2 uptake. Mitochondrial NO plays a role in cell signaling: decreased mtNOS activity leads to cell proliferation and increased mtNOS activity leads to cell arrest. Over-stimulated mtNOS activity and increased NO mitochondrial levels are associated with mitochondrial dysfunction, and nitrative and nitrosative stress under a range of pathophysiological conditions.Fil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin
Mitochondrial complex I and nitric oxide synthase as main markers of ´complex I syndrome` in Parkinson´s disease
No full textParkinson?s disease (PD) is the second most prevalent neurodegenerative disorder, and it is characterized by the progressive degeneration of the dopaminergic neurons located in the substantia nigra pars compacta, striatum body and brain cortex. Multiple -genetic and environmental- factors contribute to the appearance of PD; however, mitochondrial dysfunction with the decreased capacity to produce ATP and oxidative damage are pathognomonic characteristics always present in the affected brain areas. Mitochondrial dysfunction includes the concomitant reduction in the active respiration sustained by malate-glutamate and in the complex I activity, accompanied by changes in mtNOS biochemical (i.e. mitochondrial NO production) and functional activities, enhancement in mitochondrial O2- and H2O2 production rates, and increase in the contents of phospholipid peroxidation products and protein oxidation. Mitochondrial dynamics is also impaired in neurodegenerative diseases, not only because of the altered synthesis of new mitochondria (mitochondrial biogenesis), but also the distorted degradation of damaged mitochondria (mitophagy), making the situation even more adverse due to the accumulation of dysfunctional mitochondria. The mitochondrial dysfunction observed in PD agrees with the complex I syndrome concept, showing the high sensitivity of mitochondrial complex I to inactivation by oxidative reactions.Fil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Rukavina Mikusic, Natalia Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin
In situ and real time muscle chemiluminescence determines singlet oxygen involvement in oxidative damage during endotoxemia
Full text linkMany studies have reported the occurrence of oxidative stress in different models of sepsis, but no measurements in real time and in non-invasive manner in an acute model of endotoxemia were done, being its mechanism still under debate. In the present work, we have used in situ surface chemiluminescence to evaluate the reactive oxygen species steady-state concentrations and to identify the main chemical species involved in this phenomenon. Experimental endotoxemia provoked a twofold increase in skeletal muscle chemiluminescence (control value: 31±4cps/cm2). The use of cutoff filters and D2O and biacetyl as specific enhancers, indicates that singlet oxygen is the main emitting species in this model. This result closely correlates with elevated TBARS levels, an index of oxidative damage to lipids. Increased NO production and NADPH oxidase activity may support the formation of ONOO-, which in turn may originate HO, an initiator of the lipid oxidation chain. In summary, our data show for the first time that 1O2 is the main chemical and emitting species involved in the mechanism of oxidative stress present in an acute model of endotoxemia. This work provides new insights necessary to understand free radical mechanisms behind endotoxemic syndrome.Fil: Vanasco, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; ArgentinaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; ArgentinaFil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentin
Beneficial effects of moderate exercise on mice aging: Survival, behavior, oxidative stress, and mitochondrial electron transfer
Full text linkModerate exercise in a treadmill (10, 15, and 20 cm/s, for 5 min each, weekly) from 28 to 78 wk of age extended male and female mice life span by 19 and 9% accompanied by 36 and 13% and 13 and 9% increased performance in behavioral assays (tightrope and T-maze tests) at 52 wk of age. Moderate exercise significantly decreased the aging-associated development of oxidative stress by preventing 1) the increase in protein carbonyls and thiobarbituric acid-reactive substances contents of submitochondrial membranes; 2) the decrease in antioxidant enzyme activities (Mn- and Cu,Zn- superoxide dismutase and catalase); and 3) the decrease in mitochondrial NADH-cytochrome-c reductase and cytochrome oxidase activities observed at 52 wk of mice age in brain, heart, liver, and kidney. These effects were no longer significant at 78 wk of age in mice. Moderate exercise, started at young age in mice, increased life span, decreased oxidative stress, and prevented the decline of cytochrome oxidase activity and behavioral performance at middle age but not at old age.Fil: Navarro, Ana. Universidad de Cádiz; EspañaFil: Gomez, Carmen. Universidad de Cádiz; EspañaFil: López Cepero, José M.. Universidad de Cádiz; EspañaFil: Boveris, Alberto Antonio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin
Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production
Full text linkThis study evaluated the effect of ageing on brain mitochondrial function mediated through protein post-translational modifications. Neuronal nitric oxide synthase increased with age and this led to a discreet pattern of nitration of mitochondrial proteins. LC/MS/MS analyses identified the nitrated mitochondrial proteins as succinyl-CoA-transferase and F1-ATPase; the latter was nitrated at Tyr269, suggesting deficient ADP binding to the active site. Activities of succinyl-CoA-transferase, F1-ATPase and cytochrome oxidase decreased with age. The decreased activity of the latter cannot be ascribed to protein modifications and is most likely due to a decreased expression and assembly of complex IV. Mitochondrial protein post-translational modifications were associated with a moderately impaired mitochondrial function, as indicated by the decreased respiratory control ratios as a function of age and by the release of mitochondrial cytochrome c to the cytosol, thus supporting the amplification of apoptotic cascades.Fil: Lam, Philip Y.. University of Southern California; Estados UnidosFil: Yin, Fei. University of Southern California; Estados UnidosFil: Hamilton, Ryan T.. University of Southern California; Estados UnidosFil: Boveris, Alberto Antonio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cadenas, Enrique. University of Southern California; Estados Unido
The involvement of transition metal ions on iron-dependent lipid peroxidation
Full text linkThe metals iron (Fe) and copper (Cu) are considered trace elements, and the metals cobalt (Co) and nickel (Ni) are known as ultra-trace elements, considering their presence in low to very low quantity in humans. The biologic activity of these transition metals is associated with the presence of unpaired electrons that favor their participation in redox reactions. They are part of important enzymes involved in vital biologic processes. However, these transition metals become toxic to cells when they reach elevated tissue concentrations and produce cellular oxidative damage. Phospholipid liposomes (0.5 mg/ml, phosphatidylcholine (PC)/phosphatidylserine (PS), 60/40) were incubated for 60 min at 37°C with 25 μM of Fe2+ in the absence and in the presence of Cu2+, Co2+, and Ni2+ (0-100 μM) with and without the addition of hydrogen peroxide (H 2O2, 5-50 μM). Iron-dependent lipid peroxidation in PC/PS liposomes was assessed by thiobarbituric acid-reactive substances (TBARS) production. Metal transition ions promoted lipid peroxidation by H 2O2 decomposition and direct homolysis of endogenous hydroperoxides. The Fe2+-H2O2-mediated lipid peroxidation takes place by a pseudo-second order process, and the Cu 2+-mediated process by a pseudo-first order reaction. Co2+ and Ni2+ alone do not induce lipid peroxidation. Nevertheless, when they are combined with Fe2+, Fe2+-H2O 2-mediated lipid peroxidation was stimulated in the presence of Ni2+ and was inhibited in the presence of Co2+. The understanding of the effects of transition metal ions on phospholipids is relevant to the prevention of oxidative damage in biologic systems. © 2009 Springer-Verlag.Fil: Repetto, Marisa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; ArgentinaFil: Ferrarotti, Nidia Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin
Nitric oxide and mitochondria in metabolic syndrome
No full textNormal cardiac function is accomplished through a continuous energy supply provided by mitochondria. Heart mitochondria are the major source of reactive oxygen and nitrogen species: superoxide anion (O2-) and nitric oxide (NO). NO production by mitochondrial NOS (mtNOS) is modified by metabolic state and shows an exponential dependence on Δψ. The interaction between mtNOS and complexes I and IV might be a mechanism involved in the regulation of mitochondrial NO production. NO exerts a high affinity, reversible and physiological inhibition of cytochrome c oxidase activity. A second effect of NO on the respiratory chain is accomplished through its interaction with ubiquinol-cytochrome c oxidoreductase. The ability of mtNOS to regulate mitochondrial O2 uptake and O2 - and H2O2 productions through the interaction of NO with the respiratory chain is named mtNOS functional activity. Together, heart mtNOS allows NO to optimize the balance between cardiac energy production and utilization, and to regulate the steady-state concentrations of other oxygen and nitrogen species.Fil: Zaobornyj, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Iglesias, Dario Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Bombicino, Silvina Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentin
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