Ariel Cardoso - Academia.edu (original) (raw)

Papers by Ariel Cardoso

Cellular and Molecular Neurobiology

Obesity is associated with multiple dysfunctions including dyslipidemia, insulin resistance and d... more Obesity is associated with multiple dysfunctions including dyslipidemia, insulin resistance and diabetes. These malfunctions are associated with modifications in mitochondrial physiology. Furthermore, mitochondria are the most important site of energy metabolism and reactive oxygen species production. Alberici et al. (2006) demonstrated that hypertriglyceridemic transgenic mice display increased expression ad activity of mitochondrial ATP sensitive potassium channels (mitoK ATP), a mild uncoupling pathway, in liver. This suggests that mitoK ATP is an important adaptation to regulate body mass and metabolism. The aim of this work is to investigate the role of mitoK ATP in a high fat diet induced by soy oil supplementation, correlating changes in channel activity with metabolic and mitochondrial parameters. Mitochondria were isolated from mouse livers and serological parameters were measured for each animal. Light scattering (to estimate mitoK ATP activity), hydrogen peroxide generation, membrane potentials and oxygen consumption were measured in the mitochondrial suspensions. Our results indicate an increase in body mass, without dyslipidemia; and increases in mitoK ATP activity, in time-dependent manner, directly correlated to cholesterol levels. In addition, we found increases in ROS generation and decreased capacity of energy conversion (ADP/O) in the high fat diet group. In conclusion, our results indicate that the activity of mitoK ATP could be induced by high fat diets and that this is an novel site for metabolic and body mass control.

High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work ... more High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis occurs concomitantly with enhanced reactive oxygen species (ROS) generation, which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is a source of enhanced ROS production in mitochondria from HFD animals. This production is stimulated by the lack of NAD +. Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS.

Free radical biology & medicine

Knowledge of location and intracellular subcompartmentalization is essential for the understandin... more Knowledge of location and intracellular subcompartmentalization is essential for the understanding of redox processes, because oxidants, owing to their reactive nature, must be generated close to the molecules modified in both signaling and damaging processes. Here we discuss known redox characteristics of various mitochondrial microenvironments. Points covered are the locations of mitochondrial oxidant generation, characteristics of antioxidant systems in various mitochondrial compartments, and diffusion characteristics of oxidants in mitochondria. We also review techniques used to measure redox state in mitochondrial subcompartments, antioxidants targeted to mitochondrial subcompartments, and methodological concerns that must be addressed when using these tools.

Studies on Cardiovascular Disorders, 2010

Myocardial ischemia followed by reperfusion is a well established condition of medical importance... more Myocardial ischemia followed by reperfusion is a well established condition of medical importance in which reactive oxygen species (ROS) are determinant for the pathological outcome. Indeed, oxidative damage during reperfusion is causative of many of the complications found after ischemia. ROS leading to postischemic myocardial damage come from many sources, including mitochondria, NADPH oxidase, xanthine oxidase, and infiltrated phagocytes [1]. ROS also can act as signaling molecules in the cardiovascular system, including protecting the heart against myocardial ischemic damage, secondarily to ischemic pre- and postconditioning. In this case, there is ample evidence that the source of signaling ROS is mitochondrial [2–7]. This chapter will briefly review aspects of mitochondrial ROS signaling relevant to myocardial ischemic protection by pre- and postconditioning.

PLoS ONE, 2013

High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work ... more High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis is accompanied by enhanced generation of reactive oxygen species (ROS), which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is also a source of ROS production in mitochondria of HFD animals. This production is stimulated by the lack of NAD + . Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS.

Journal of Bioenergetics and Biomembranes, 2010

High fat diets are extensively associated with health complications within the spectrum of the me... more High fat diets are extensively associated with health complications within the spectrum of the metabolic syndrome. Some of the most prevalent of these pathologies, often observed early in the development of high-fat dietary complications, are non-alcoholic fatty liver diseases. Mitochondrial bioenergetics and redox state changes are also widely associated with alterations within the metabolic syndrome. We investigated the mitochondrial effects of a high fat diet leading to non-alcoholic fatty liver disease in mice. We found that the diet does not substantially alter respiratory rates, ADP/O ratios or membrane potentials of isolated liver mitochondria. However, H 2 O 2 release using different substrates and ATP-sensitive K + transport activities are increased in mitochondria from animals on high fat diets. The increase in H 2 O 2 release rates was observed with different respiratory substrates and was not altered by modulators of mitochondrial ATP-sensitive K + channels, indicating it was not related to an observed increase in K + transport. Altogether, we demonstrate that mitochondria from animals with diet-induced steatosis do not present significant bioenergetic changes, but display altered ion transport and increased oxidant generation. This is the first evidence, to our knowledge, that ATP-sensitive K + transport in mitochondria can be modulated by diet. Keywords Steatosis . Respiration . Mitochondrial bioenergetics . Mitochondrial ATP-sensitive potassium channels (mitoK ATP ) . Reactive oxygen species (ROS) Abbreviations ATP Adenosine triphosphate DZX Diazoxide 5-HD 5-hydroxydecanoate MS Metabolic syndrome mitoK ATP Mitochondrial ATP-sensitive potassium channels MPT Mitochondrial permeability transition NAFLD Non-alcoholic fatty liver diseases ROS Non-alcoholic steatohepatitis (NASH), reactive oxygen species A. R. Cardoso :

Free Radical Biology and Medicine, 2012

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2010

Mitochondria are the central coordinators of energy metabolism and alterations in their function ... more Mitochondria are the central coordinators of energy metabolism and alterations in their function and number have long been associated with metabolic disorders such as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation requires an electrochemical gradient across the inner mitochondrial membrane, ion channels in this membrane certainly must play an important role in the regulation of energy metabolism. However, in many experimental settings, the relationship between the activity of mitochondrial ion transport and metabolic disorders is still poorly understood. This review briefly summarizes some aspects of mitochondrial H + transport (promoted by uncoupling proteins, UCPs), Ca 2+ and K + uniporters which may be determinant in metabolic disorders.

Cellular and Molecular Neurobiology

Obesity is associated with multiple dysfunctions including dyslipidemia, insulin resistance and d... more Obesity is associated with multiple dysfunctions including dyslipidemia, insulin resistance and diabetes. These malfunctions are associated with modifications in mitochondrial physiology. Furthermore, mitochondria are the most important site of energy metabolism and reactive oxygen species production. Alberici et al. (2006) demonstrated that hypertriglyceridemic transgenic mice display increased expression ad activity of mitochondrial ATP sensitive potassium channels (mitoK ATP), a mild uncoupling pathway, in liver. This suggests that mitoK ATP is an important adaptation to regulate body mass and metabolism. The aim of this work is to investigate the role of mitoK ATP in a high fat diet induced by soy oil supplementation, correlating changes in channel activity with metabolic and mitochondrial parameters. Mitochondria were isolated from mouse livers and serological parameters were measured for each animal. Light scattering (to estimate mitoK ATP activity), hydrogen peroxide generation, membrane potentials and oxygen consumption were measured in the mitochondrial suspensions. Our results indicate an increase in body mass, without dyslipidemia; and increases in mitoK ATP activity, in time-dependent manner, directly correlated to cholesterol levels. In addition, we found increases in ROS generation and decreased capacity of energy conversion (ADP/O) in the high fat diet group. In conclusion, our results indicate that the activity of mitoK ATP could be induced by high fat diets and that this is an novel site for metabolic and body mass control.

High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work ... more High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis occurs concomitantly with enhanced reactive oxygen species (ROS) generation, which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is a source of enhanced ROS production in mitochondria from HFD animals. This production is stimulated by the lack of NAD +. Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS.

Free radical biology & medicine

Knowledge of location and intracellular subcompartmentalization is essential for the understandin... more Knowledge of location and intracellular subcompartmentalization is essential for the understanding of redox processes, because oxidants, owing to their reactive nature, must be generated close to the molecules modified in both signaling and damaging processes. Here we discuss known redox characteristics of various mitochondrial microenvironments. Points covered are the locations of mitochondrial oxidant generation, characteristics of antioxidant systems in various mitochondrial compartments, and diffusion characteristics of oxidants in mitochondria. We also review techniques used to measure redox state in mitochondrial subcompartments, antioxidants targeted to mitochondrial subcompartments, and methodological concerns that must be addressed when using these tools.

Studies on Cardiovascular Disorders, 2010

Myocardial ischemia followed by reperfusion is a well established condition of medical importance... more Myocardial ischemia followed by reperfusion is a well established condition of medical importance in which reactive oxygen species (ROS) are determinant for the pathological outcome. Indeed, oxidative damage during reperfusion is causative of many of the complications found after ischemia. ROS leading to postischemic myocardial damage come from many sources, including mitochondria, NADPH oxidase, xanthine oxidase, and infiltrated phagocytes [1]. ROS also can act as signaling molecules in the cardiovascular system, including protecting the heart against myocardial ischemic damage, secondarily to ischemic pre- and postconditioning. In this case, there is ample evidence that the source of signaling ROS is mitochondrial [2–7]. This chapter will briefly review aspects of mitochondrial ROS signaling relevant to myocardial ischemic protection by pre- and postconditioning.

PLoS ONE, 2013

High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work ... more High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis is accompanied by enhanced generation of reactive oxygen species (ROS), which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is also a source of ROS production in mitochondria of HFD animals. This production is stimulated by the lack of NAD + . Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS.

Journal of Bioenergetics and Biomembranes, 2010

High fat diets are extensively associated with health complications within the spectrum of the me... more High fat diets are extensively associated with health complications within the spectrum of the metabolic syndrome. Some of the most prevalent of these pathologies, often observed early in the development of high-fat dietary complications, are non-alcoholic fatty liver diseases. Mitochondrial bioenergetics and redox state changes are also widely associated with alterations within the metabolic syndrome. We investigated the mitochondrial effects of a high fat diet leading to non-alcoholic fatty liver disease in mice. We found that the diet does not substantially alter respiratory rates, ADP/O ratios or membrane potentials of isolated liver mitochondria. However, H 2 O 2 release using different substrates and ATP-sensitive K + transport activities are increased in mitochondria from animals on high fat diets. The increase in H 2 O 2 release rates was observed with different respiratory substrates and was not altered by modulators of mitochondrial ATP-sensitive K + channels, indicating it was not related to an observed increase in K + transport. Altogether, we demonstrate that mitochondria from animals with diet-induced steatosis do not present significant bioenergetic changes, but display altered ion transport and increased oxidant generation. This is the first evidence, to our knowledge, that ATP-sensitive K + transport in mitochondria can be modulated by diet. Keywords Steatosis . Respiration . Mitochondrial bioenergetics . Mitochondrial ATP-sensitive potassium channels (mitoK ATP ) . Reactive oxygen species (ROS) Abbreviations ATP Adenosine triphosphate DZX Diazoxide 5-HD 5-hydroxydecanoate MS Metabolic syndrome mitoK ATP Mitochondrial ATP-sensitive potassium channels MPT Mitochondrial permeability transition NAFLD Non-alcoholic fatty liver diseases ROS Non-alcoholic steatohepatitis (NASH), reactive oxygen species A. R. Cardoso :

Free Radical Biology and Medicine, 2012

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2010

Mitochondria are the central coordinators of energy metabolism and alterations in their function ... more Mitochondria are the central coordinators of energy metabolism and alterations in their function and number have long been associated with metabolic disorders such as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation requires an electrochemical gradient across the inner mitochondrial membrane, ion channels in this membrane certainly must play an important role in the regulation of energy metabolism. However, in many experimental settings, the relationship between the activity of mitochondrial ion transport and metabolic disorders is still poorly understood. This review briefly summarizes some aspects of mitochondrial H + transport (promoted by uncoupling proteins, UCPs), Ca 2+ and K + uniporters which may be determinant in metabolic disorders.