Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2-mediated oxidative insult in H9C2 myocardial cells

AbstractCarvedilol, a β-adrenoreceptor antagonist with strong antioxidant activity, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Although growing evidences suggest specific effects on mitochondrial metabolism, how carvedilol would exert its overall activity has not been completely disclosed. In the present work we have investigated the impact of carvedilol-treatment on mitochondrial bioenergetic functions and ROS metabolism in H9C2 cells. This analysis has revealed a dose-dependent decrease in respiratory fluxes by NAD-dependent substrates associated with a consistent decline of mitochondrial complex I activity. These changes were associated with an increase in mitochondrial H2O2 production, total glutathione and protein thiols content. To evaluate the antioxidant activity of carvedilol, the effect of the exposure of control and carvedilol-pretreated H9C2 cells to H2O2 were investigated. The H2O2-mediated oxidative insult resulted in a significant decrease of mitochondrial respiration, glutathione and protein thiol content and in an increased level of GSSG. These changes were prevented by carvedilol-pretreatment. A similar protective effect on mitochondrial respiration could be obtained by pre-treatment of the cells with a sub-saturating amount of rotenone, a complex I inhibitor.We therefore suggest that carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning-like mechanism, via inhibition of mitochondrial complex I

Tissue-specific changes of mitochondrial functions in aged rats: Effect of a long-term dietary treatment with N-acetylcysteine

The understanding of the involvement of mitochondrial oxidative phosphorylation (OXPHOS) in the aging process has often been biased by the different methodological approaches as well as the choice of the biological material utilized by the various groups. In the present paper, we have carried out a detailed analysis of several bioenergetic parameters and oxidative markers in brain and heart mitochondria from young (2 months) and old (28 months) rats. This analysis has revealed an age-related decrease in respiratory fluxes in brain but not in heart mitochondria. The age-related decrease in respiratory rate (-43%) by NAD-dependent substrates was associated with a consistent decline (-40%) of complex I activity in brain mitochondria. On the other hand, heart mitochondria showed an age-related decline of complex II activity. Both tissues showed, however, an age-associated accumulation of oxidative damage. We have then performed the same analysis on old (28 months) rats subjected to a long-term (16 months) diet containing the antioxidant N-acetylcysteine (NAC). The treated old rats showed a slight brain-specific improvement of mitochondrial energy production efficiency, mostly with NAD-dependent substrates, together with a decrease in carbonyl protein content and an increase in the amount of protein thiols of brain cytosolic fraction. A full recovery of complex II activity was detected in heart mitochondria from NAC-treated old rats. The present work documents the marked tissue specificity of the decline of bioenergetic functions in isolated mitochondria from aged rats and provides the first data on the effects of a long-term treatment with N-acetylcysteine. © 2004 Elsevier Inc. All rights reserved

Territorios segregados y (des)Gobernanza Urbana: Nápoles/Madrid/Barcelona

El presente documento recoge los resultados de las Jornadas de investigación Territorios segregados y (des) Gobernanza urbana celebradas los días 9 y 10 de octubre 2019 en la Escuela Técnica Superior de Arquitectura organizadas por el Grupo de investigación en Arquitectura, Urbanismo y sostenibilidad (giau+s) de la Universidad Politécncia de Madrid, el Departamento de Urbanística y Ordenación del Territorio (DUyOT), de la Universidad Politécnica de Madrid; y el Centro Interdipartimentale di Ricerca L.U.P.T. – Laboratorio di Urbanistica e di Pianificazione Territoriale “Raffaele d’Ambrosio” (LUPT) de la Università degli Studi di Napoli, en el marco del Convenio de colaboración cultural y científica entre la Universitá degli Studi di Napoli Federico II y la Universidad Politécnica de Madrid El objetivo de las jornada era la reflexión y puesta en común de diversos trabajos de investigación realizados por los componentes de tres grupos de investigación que trabajan en líneas complementarias desde tres territorios: Barcelona, Madrid y Nápoles, como punto de inicio para establecer una línea de colaboración conjunta sobre los retos a los que se enfrentan las áreas urbanas y los territorios en torno a su gobernanza y gestión, en contextos cada vez más complejos afectados por dinámicas de segregación socio-espacial y vulnerabilidad crecientes. Esta publicación colectiva se enmarca en este proyecto conjunto de puesta en común y difusión de los resultados de las investigaciones de los tres grupos: Grupo de investigación en Arquitectura, Urbanismo y sostenibilidad (giau+s) de la Universidad Politécncia de Madrid, Centro Interdipartimentale di Ricerca L.U.P.T. – Laboratorio di Urbanistica e di Pianificazione Territoriale “Raffaele d’Ambrosio” (LUPT) de la Università degli Studi di Napoli y el Grup d'Estudis sobre Energia Territori i Societat (GURB) de la Universidad Autónoma de Barcelon