Home The redox environment inside cells is very different to that outside the cell, and it is clear that many extracellular environments are both more oxidizing and also subject to extensive oxidation. This difference in redox environments results in significant changes in oxidation chemistry and biology, altered redox equilibria, and antioxidant defense mechanisms. Oxidation events outside cells also play a critical role in driving many diseases, particularly in fibrotic pathologies. Many extracellular proteins are highly abundant, long-lived and relatively poorly protected against damage. They can therefore accumulate high levels of modification during ageing and disease, resulting in their increasing use as biomarkers of long-term oxidative stress. However, these extracellular modifications are not always innocent bystanders as oxidized extracellular matrix and glycocalyx materials are increasingly recognized to play a key role in determining cell function and fate. Extracellular oxidation is critical for acute cellular responses, tissue assembly and development, and specific and localized oxidation is essential to life, particularly with regard to tissue architecture and function. Deliberate exogenous oxidant formation also appears to be a promising method of repairing tissue damage, with animal and human trials indicating that controlled oxidation can be of major therapeutic use in tissue repair after injury. This session will examine extracellular oxidation induced by both peroxidases and nitration/nitrosylation systems from chemistry through to the bedside with a particular emphasis on cancer and neurodegeneration and cardiovascular disease.
Chairs: Michael J. Davies, D.Phil, University of Copenhagen - DK & Andreia Chignalia, PhD, University of Arizona - USA
Oxidative DNA damage is a constant challenge of the genome, arising from exposure to reactive oxygen species (ROS). These can come from multiple external and internal sources, including but not limited to endogenous chemical processes through the cells’ own metabolism and enzymatic activity, inflammatory processes, toxins, or ionizing radiation. When persistent, damage harbors the risk of disrupting cellular function and causing mutation. Naturally, living organisms have evolved very efficient repair mechanisms. Mitochondrial overproduction of ROS is the underlying cause for oxidative stress related cell damage and its role in mutagenesis has long been postulated. On the other hand, exploiting excessive oxidative DNA damage that promote cancer cell death has emerged as promising anti-cancer therapy. This session will shed some light on our current understandings on the role of ROS-induced DNA damage in disease.
Chairs: Carola Neumann, MD, University of Pittsburgh - USA & Albert van der Vliet, PhD, University of Vermont - USA
Oxidative stress contributes to pathophysiological mechanisms of acute and chronic conditions (i.e., cancers, sepsis, and neurological diseases, aging). The ability to monitor redox state has great potential as a clinical tool for assessing disease state and the activity of redox therapeutics. Although blood is the most collected biospecimen, its current usefulness for redox investigations is limited since it is prone to oxidative changes and generation of artifactual redox reactive species post-collection. Thus, it is critical to develop innovative collection methods that capture and preserve the endogenous redox state of specimens. Artifacts associated with collection and processing of blood specimens can result in erroneous interpretation of the targeted redox species, negatively impacting the study of disease mechanisms. Therefore, the development of improved methods for the preservation and storage of biological samples plays a fundamental role in the pre-analytical phase of any study. The focus of this session will be on new approaches for preventing artifactual oxidation and loss of specimen integrity during sample processing and storage such that accurate analytical analyses are possible to allow for informed interpretation of patients redox metabolism. Presenters will highlight current and innovative methods for collection, processing, and analysis of redox biomarkers focusing on blood specimens.
Chairs: Cristina Furdui, PhD, Wake Forest University - USA & Daniel Kim-Shapiro, PhD, Wake Forest University - USA
The role of bioactive lipids in inflammatory processes, their identification, detection, and quantification are relevant areas of study for the biochemistry and physiology of inflammatory processes. They are related to health disease processes. It is intended to address the current state of the art of methodologies applied to the study of lipid mediators in vitro, cellular systems, and human samples. In particular, the latest advances in mass spectrometry techniques, HPLC, as well as in the transcriptomic, proteomic, and metabolomic analysis of signaling pathways associated with changes in the levels of lipid mediators and their role in pathologies such as cardiovascular, pulmonary, and neurodegenerative diseases. Electrophilic mediators exert signaling actions by covalently modifying key proteins and modulating relevant signaling pathways. Among these lipids, nitrated fatty acids, ketones, and epoxides derived from enzymatic and nonenzymatic sources are part of the activation and regulation of intracellular cascades. The formation and biological activities of the specialized pro-resolving lipid mediators (SPM) is a relevant area of study being highly discussed in academia and literature. SPMs have been shown to exert protective effects on different pathologies, mainly those associated with inflammatory processes. The symposium will address the role that lipid-derived bioactive compounds play in the development and treatment of human diseases, from their formation, and signaling to their final protective effects. The primary objective is to bring together experts and researchers from diverse disciplines to discuss and share insights into the dynamic interplay between lipidomics, oxidative stress, and their implications for human health and disease.
Chairs: Andres Trostchansky, PhD, Universidad de la Republica - Uruguay & Stacy Gelhaus Wendell, PhD, University of Pittsburgh
A fundamental challenge for the medical-scientific community is to enable aging with the greatest independence and quality of life possible. In this sense, functional performance in older people is the factor most strongly related to quality of life and the risk of hospitalization, permanent institutionalization, use of social and health resources, and death. Despite advanced age, some persons remain vigorous, while others have a gradual functional decline in the absence of apparent diseases. Unlocking the mechanistic foundation of age-associated diseases requires understanding the cellular and molecular mechanisms underlying organic deterioration, both during normal aging and in chronic diseases or unhealthy lifestyles. One of the twelve hallmarks of aging is mitochondrial dysfunction. Mitochondria produce most of the cellular ATP and are also involved in other essential cellular functions such as reactive oxygen species signaling, calcium homeostasis, inflammation, and even cell death. Numerous studies have described damage to mitochondria in aged cells and organisms, including humans. Emerging evidence suggests that reduced skeletal muscle oxidative capacity and efficiency underlie the etiology of mobility loss, diminished muscle strength, and performance in older adults. Moreover, inefficient and dysfunctional mitochondria in the central nervous system have been implicated in neurodegenerative diseases. However, the factors that are associated with mitochondrial dysfunction have not been well characterized and no data connects age-related changes in mitochondrial dysfunction with phenotypic and pathological changes in aging. In this symposium, we aim to understand the fundamental aspects of ageassociated mitochondrial dysfunction, its relation with the functional status of individuals, and the role of different types of interventions in the maintenance of these organelles.
Chairs: Mari Carmen Gomez-Cabrera, University of Valencia - Spain & Giovanni E. Mann, King’s College London - UK
Cardiac and skeletal muscle (striated muscle) are crucial for our ability to pump blood, breathe, and move. They are metabolically demanding organs packed with mitochondria that are key for redox signaling and metabolic adaptation. The capacity of striated muscle to adapt to stimuli and produce force is largely dependent on the function and health of its mitochondria. Moreover, mitochondria utilize signaling molecules and metabolic intermediates to modulate: the expression of nuclear genes (retrograde signaling), posttranslational modifications (e.g. oxidation), and cell apoptosis/survival pathways. Thus, impaired mitochondrial function may be the most important factor in the progression of muscle decline associated with chronic disease and ageing. In this symposium, we will highlight the most recent understandings of how alterations in the mitochondrial interplay contribute to muscle dysfunction.
Chairs: Johanna Lanner, PhD, Karolinska Institutet - Sweden & Holly Van Remmen, PhD, Oklahoma Medical Research Fnd - USA
Our understanding of hydrogen sulfide (H2S) and related derivatives such as persulfides (RSSH/RSS-) have rapidly advanced. This symposium will provide an update on new aspects of redox biology that is governed by redox-active sulfur and sulfide containing molecules, with a special focus on chemical tools for understanding reactive sulfur and sulfide species to molecular signalling and biological functions.
Chairs: Hozumi Motohashi, MD, PhD, Tohoku University - Japan & Melanie Madhani, PhD, University of Birmingham - UK
Recent advancements in single-cell analysis techniques and the development of cell-specific knockout (KO) and knock-in (KI) mice models have paved the way for groundbreaking discoveries on unexpected roles of nitric oxide (NO) in systemic redox metabolism and cell differentiation. The Isakson Lab discovered the critical role of non-erythrocytic hemoglobin in myoendothelial junctions, acting as a NO scavenger and thereby controlling vascular NO bioavailability and vasodilation under normoxic conditions. Utilizing endothelial cell (EC)-specific KO his lab found that non-erythrocytic hemoglobin under hypoxic conditions is a nitrite reductase, and thereby regulates vascular tone and blood pressure. In recent unpublished investigations they employed EC-specific caveolin and eNOS KO mice, alongside human cells and single-cell sequencing from patients with adiposity. They identified a novel NO-mediated signaling pathway that orchestrates the trafficking of free fatty acids within and outside adipose tissue endothelial cells. This pathway plays a crucial role in regulating circulating lipids, offering new perspectives on the metabolic functions of NO. The Cortese-Krott lab research work recently revealed an unexpected role of red cell endothelial nitric oxide synthase (eNOS) for the control of blood pressure and cardioprotection. This function is distinct from the well-known role of EC eNOS, highlighting the importance of cell-specific approach to understand NO signaling. Moreover, the Cortese-krott lab recently generated erythroid cell-specific soluble guanylate cyclase (sGC) KO mice and found that red cell sGC is pivotal for early erythropoiesis and blood pressure control. This discovery reveal a novel role of NO-mediated sGC regulation in hematological and cardiovascular diseases, suggesting potential therapeutic targets. This session will provide a comprehensive overview of the cell-specific roles of NO/reactive species in redox metabolism and cell differentiation. Through cutting-edge research and innovative methodologies, attendees will gain insights into the complex regulatory mechanisms of reactive species and their implications for human health.
Chairs: Neil Hogg, PhD, Medical College of Wisconsin - USA & Brant Isakson, PhD, University of Virginia - USA
Heme proteins are pivotal for the biology of reactive oxygen and nitrogen species (ROS/RNS). Through their role in oxygen transport and delivery, oxidative phosphorylation, nitric oxide synthesis or the generation of ROS/RNS, these proteins appear in almost every biological free radical-related pathway. Heme proteins include some of the most researched proteins in biology -myoglobin and hemoglobin. Despite the longstanding interest in heme proteins, novel vertebrate heme proteins -neuroglobin, cytoglobin, androglobin- have been discovered in the last 25 years, and the known globins have been found in unsuspected tissues and cellular locations, challenging our existing knowledge. In this session we focus on recent advances that challenge the general conceptions about the role of heme proteins in chemical biology, from roles in development to vascular biology and beyond.
Chairs: Jesus Tejero, PhD, University of Pittsburgh - USA & David Jourd'heuil, PhD, Albany Medical College - USA
Epigenetics and epigenetic sequencing techniques have been at the leading edge of science for the past decade. Understanding how the genome is regulated via noncoding RNAs and structural organization of chromatin is critical to the advancement of medicine and the development of new therapeutics. Recent evidence has revealed redox-mediated signaling as well as direct redox modifications of chromatin. This symposium will touch on cutting edge discoveries as to how redox regulation of the epigenome contributes to health and disease across multiple tissues/ cell types.
Chairs: Evan DeVallance, PhD, West Virginia University - USA & Nirmal Kumar, PhD, University of North Dakota - USA
At the center of redox signaling are oxidoreductive chemical reactions involving low and moderate localized levels of reactive oxygen species and reductants that modify the thiol-side chain of cysteinyl residues in proteins. In turn, these post-translational modifications cause a spectrum of structural alterations that allow reactive oxygen species production to be coupled to functional outputs in the cell. This session discusses timely and exciting advances in the redox field that highlight the compartmentalization of redox signaling events and recent translational efforts to develop small molecules that target cysteines and other nucleophilic residues.
Chairs: Ben Boivin, PhD, University at Albany - USA & Nathalie Grandvaux, PhD, University of Montreal - Canada
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