- Email: [email protected]
Ultra-long-distance running and the liver
S14
M. Casal / Free Radical Biology and Medicine 120 (2018) S6–S23
emerging evidence for a role in maintaining whole body proteostasis that appear to be important in their impact on organismal ageing.
E-mail address: [email protected]
molecular events with a kinetic, quantitative and systemic view and connect redox/free radical biochemistry with biological outcomes.
E-mail address: [email protected]
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.059
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.062
L-32
L-34
Ultra-long-distance running and the liver
Quantitative analysis of cytosolic and mitochondrial H2O2 metabolism and toxicity in human epithelial cells
Zsolt Radak Hadley D. Sikes University of Physical Education, Budapest, Hungary Massachusetts Institute of Technology, Cambridge, MA, USA Regular exercise attenuates the age associated decline in VO2max, functional impairment in different organs, production of reactive oxygen species (ROS) and the related oxidative damage. Although regular exercise attenuates the age-associated decline in VO2max and deterioration of most of the organs via enhanced mitochondrial function and dynamics the effects are complex and mediated by multi signaling pathways. Exercise training attenuates the age-related loss in cellular housekeeping system, which includes proteasome, Lon protease, autophagy, mitophagy and DNA repair systems which beneficially impacts organ function. Accumulating evidence suggests that exercise lessen the deleterious effects of aging, however it seems unlikely that the systemic effects are mediated through a specific biomarker.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.061
Hydrogen peroxide has long been recognized as a signaling molecule due to its selective reactivity with particular cysteine residues of a subset of proteins. Changes in its concentration as a function of time and space within the cell can determine cellular fates, and different cell types may exhibit differing responses to identical increases in hydrogen peroxide flux. These observations form the basis for pro-oxidant chemotherapeutics in the treatment of cancer. However, many questions remain regarding the molecular mechanisms of hydrogen peroxide-mediated signaling pathways, the magnitudes of differences among cell types, and the impact of localization within the cell. A mathematical model of the reactivity and transport of H2O2 within human epithelial cells will be presented and used to address these questions.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.063
L-33
Superoxide radical-nitric oxide interplay and the fate of peroxynitrite in biological systems Rafael Radi 1,2 1
Departamento de Bioquímica, Facultad de Medicina, Montevideo, Uruguay 2 Center for Free Radical and Biomedical Research (CEINBIO), Universidad de la República, Montevideo, Uruguay
In aerobic organisms, the biological fluxes of O2- are large, typically ZμM/s in various cell compartments. In spite of remarkable high formation rates, the steady-state concentrations of O2- are kept very low due to the superefficient enzymatic catalysis of O2- dismutation by SOD. In this context, NO can outcompete the SOD-catalyzed reaction, via its diffusion-controlled reaction with O2-, and yield peroxynitrite. In turn, peroxynitrite, an oxidant and nucleophile, can readily react with a variety of molecular targets most notably peroxiredoxins and CO2, in processes that compete between detoxification and the trigger of free radical chemistry. As the pKa of peroxynitrite is 6.8, the biochemistry of peroxynitrite is highly pH-dependent in biological milieu. A relevant subcellular site where the O2-/NO interplay becomes critical is the mitochondrion where subtle kinetic and redox balances involve MnSOD and its nitration and inactivation by peroxynitrite. Also, the phagosome constitutes a key compartment for these interactions during infection processes involving intracellular pathogens. The aim of the presentation is to integrate these
L-35
Identification and quantification of protein damage induced by inflammatory oxidants Michael J. Davies University of Copenhagen, Copenhagen, Denmark
Proteins are major oxidant targets due to their abundance and their high rate constants for reaction with oxidants generated at sites of inflammation (e.g. O2-, H2O2, HOCl, ONOOH). It is now clear that there are large variations in the nature and extent of damage induced by different oxidants due to the large variation in the kinetics and selectivity of these species. With reactive oxidants, such as HOCl and ONOOH, both sidechain (mainly at Cys, Met, Trp, Tyr and His) and backbone damage can be detected, whereas with less reactive species, such as O2- and H2O2 damage is both limited and highly selective. Protein damage within cells can, in many cases, be repaired, or removed rapidly via catabolism. External to cells, the situation is somewhat different. Extracellular matrix (ECM) proteins can be highly abundant (e.g. elastin is 50% of arteries by dry mass), are poorly protected against damage and have long half-lives, and therefore can accumulate high levels of modification with increasing age and disease. Some ECM proteins have unusual amino acid compositions, and this can result in altered extents, and types, of damage. Recent data
M. Casal / Free Radical Biology and Medicine 120 (2018) S6–S23
emerging evidence for a role in maintaining whole body proteostasis that appear to be important in their impact on organismal ageing.
E-mail address: [email protected]
molecular events with a kinetic, quantitative and systemic view and connect redox/free radical biochemistry with biological outcomes.
E-mail address: [email protected]
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.059
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.062
L-32
L-34
Ultra-long-distance running and the liver
Quantitative analysis of cytosolic and mitochondrial H2O2 metabolism and toxicity in human epithelial cells
Zsolt Radak Hadley D. Sikes University of Physical Education, Budapest, Hungary Massachusetts Institute of Technology, Cambridge, MA, USA Regular exercise attenuates the age associated decline in VO2max, functional impairment in different organs, production of reactive oxygen species (ROS) and the related oxidative damage. Although regular exercise attenuates the age-associated decline in VO2max and deterioration of most of the organs via enhanced mitochondrial function and dynamics the effects are complex and mediated by multi signaling pathways. Exercise training attenuates the age-related loss in cellular housekeeping system, which includes proteasome, Lon protease, autophagy, mitophagy and DNA repair systems which beneficially impacts organ function. Accumulating evidence suggests that exercise lessen the deleterious effects of aging, however it seems unlikely that the systemic effects are mediated through a specific biomarker.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.061
Hydrogen peroxide has long been recognized as a signaling molecule due to its selective reactivity with particular cysteine residues of a subset of proteins. Changes in its concentration as a function of time and space within the cell can determine cellular fates, and different cell types may exhibit differing responses to identical increases in hydrogen peroxide flux. These observations form the basis for pro-oxidant chemotherapeutics in the treatment of cancer. However, many questions remain regarding the molecular mechanisms of hydrogen peroxide-mediated signaling pathways, the magnitudes of differences among cell types, and the impact of localization within the cell. A mathematical model of the reactivity and transport of H2O2 within human epithelial cells will be presented and used to address these questions.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.063
L-33
Superoxide radical-nitric oxide interplay and the fate of peroxynitrite in biological systems Rafael Radi 1,2 1
Departamento de Bioquímica, Facultad de Medicina, Montevideo, Uruguay 2 Center for Free Radical and Biomedical Research (CEINBIO), Universidad de la República, Montevideo, Uruguay
In aerobic organisms, the biological fluxes of O2- are large, typically ZμM/s in various cell compartments. In spite of remarkable high formation rates, the steady-state concentrations of O2- are kept very low due to the superefficient enzymatic catalysis of O2- dismutation by SOD. In this context, NO can outcompete the SOD-catalyzed reaction, via its diffusion-controlled reaction with O2-, and yield peroxynitrite. In turn, peroxynitrite, an oxidant and nucleophile, can readily react with a variety of molecular targets most notably peroxiredoxins and CO2, in processes that compete between detoxification and the trigger of free radical chemistry. As the pKa of peroxynitrite is 6.8, the biochemistry of peroxynitrite is highly pH-dependent in biological milieu. A relevant subcellular site where the O2-/NO interplay becomes critical is the mitochondrion where subtle kinetic and redox balances involve MnSOD and its nitration and inactivation by peroxynitrite. Also, the phagosome constitutes a key compartment for these interactions during infection processes involving intracellular pathogens. The aim of the presentation is to integrate these
L-35
Identification and quantification of protein damage induced by inflammatory oxidants Michael J. Davies University of Copenhagen, Copenhagen, Denmark
Proteins are major oxidant targets due to their abundance and their high rate constants for reaction with oxidants generated at sites of inflammation (e.g. O2-, H2O2, HOCl, ONOOH). It is now clear that there are large variations in the nature and extent of damage induced by different oxidants due to the large variation in the kinetics and selectivity of these species. With reactive oxidants, such as HOCl and ONOOH, both sidechain (mainly at Cys, Met, Trp, Tyr and His) and backbone damage can be detected, whereas with less reactive species, such as O2- and H2O2 damage is both limited and highly selective. Protein damage within cells can, in many cases, be repaired, or removed rapidly via catabolism. External to cells, the situation is somewhat different. Extracellular matrix (ECM) proteins can be highly abundant (e.g. elastin is 50% of arteries by dry mass), are poorly protected against damage and have long half-lives, and therefore can accumulate high levels of modification with increasing age and disease. Some ECM proteins have unusual amino acid compositions, and this can result in altered extents, and types, of damage. Recent data