An Nrf1- and Nrf2-related Transcription Factor, Cnc-C, Mediates Multiple Stress Responses in Drosophila Melanogaster PDF Download
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Author: Min Tian Publisher: ISBN: Category : Languages : en Pages : 144
Book Description
Ineffective cellular stress responses contribute to the development of multiple diseases. A family of the highly conserved transcription factors represented by Cnc proteins in Drosophila and Nrf proteins in mammals includes important mediators of such stress responses. One such protein, mammalian, Nrf2, is a master regulator of oxidative stress defense genes. The related Nrf1 protein, in contrast plays an important role in preventing or ameliorating unfolded protein stress and maintaining effective proteasomal protein degradation. The cap’n’collar (cnc) gene encodes the sole member of this family in Drosophila. Work by the Bohmann lab has previously shown the Cnc C-splice form, CncC, to be a functional homolog of Nrf2 and to regulate the expression of many antioxidant genes in response to oxidative stress. No other cnc family gene is present in the Drosophila genome and whether a fly homolog of Nrf1 exists had remained unclear. I and others, however, noticed, sequence similarities between CncC and Nrf1, raising the possibility that the Drosophila cnc locus encodes one or several proteins that combine the functions of Nrf1 and Nrf2. Here, I provide evidence in support of this hypothesis. I show that CncC mediates the transcriptional response to oxidative stress and proteasome dysfunction by two distinct mechanisms. I show that the activation of CncC in response to impaired proteasome function requires the aspartic protease Rings Lost (Rngo) and Nglycanase 1 (Ngly1). Intriguingly, since a recessive mutation of the human ngly1 gene is the cause of a rare neurological syndrome (N-glycanase deficiency), loss of Nrf1 function may contribute to the pathology of this disease. My work establishes Drosophila CncC as an interesting model to study the interplay and coordination of the cellular responses to proteotoxic and oxidative stresses. Taking advantage of the Drosophila system to investigate the biology of the Nrf protein family may thus contribute to the understanding of human diseases that are associated with cellular stress, possibly including N-glycanase deficiency. The second chapter of my thesis focuses on the relationship between high sugar diet, obesity and oxidative stress. It has been shown that obesity is associated with increased oxidative stress in multiple tissues. This increased oxidative stress can be caused by either increased ROS production or decreased antioxidant mechanisms. While it has been shown that overnutrition increases ROS production in mitochondria, how nutrition surplus affects antioxidant defense pathways is less well understood. I hypothesized that nutrition surplus compromises the oxidative stress defense. To explore this idea, I established an obesity model in which Drosophila is exposed to a high-sucrose diet. Consistent with the starting hypothesis, I found that high-sucrose food suppresses the fly’s oxidative stress defense. Further experiments are needed to understand the molecular mechanism by which high-sucrose diet reduces antioxidant responses. My experiments establish a connection between high-sucrose diet and oxidative stress defense and demonstrate the advantage of using the fruit fly as an animal model to study the health effects of obesity and related metabolic diseases.
Author: Min Tian Publisher: ISBN: Category : Languages : en Pages : 144
Book Description
Ineffective cellular stress responses contribute to the development of multiple diseases. A family of the highly conserved transcription factors represented by Cnc proteins in Drosophila and Nrf proteins in mammals includes important mediators of such stress responses. One such protein, mammalian, Nrf2, is a master regulator of oxidative stress defense genes. The related Nrf1 protein, in contrast plays an important role in preventing or ameliorating unfolded protein stress and maintaining effective proteasomal protein degradation. The cap’n’collar (cnc) gene encodes the sole member of this family in Drosophila. Work by the Bohmann lab has previously shown the Cnc C-splice form, CncC, to be a functional homolog of Nrf2 and to regulate the expression of many antioxidant genes in response to oxidative stress. No other cnc family gene is present in the Drosophila genome and whether a fly homolog of Nrf1 exists had remained unclear. I and others, however, noticed, sequence similarities between CncC and Nrf1, raising the possibility that the Drosophila cnc locus encodes one or several proteins that combine the functions of Nrf1 and Nrf2. Here, I provide evidence in support of this hypothesis. I show that CncC mediates the transcriptional response to oxidative stress and proteasome dysfunction by two distinct mechanisms. I show that the activation of CncC in response to impaired proteasome function requires the aspartic protease Rings Lost (Rngo) and Nglycanase 1 (Ngly1). Intriguingly, since a recessive mutation of the human ngly1 gene is the cause of a rare neurological syndrome (N-glycanase deficiency), loss of Nrf1 function may contribute to the pathology of this disease. My work establishes Drosophila CncC as an interesting model to study the interplay and coordination of the cellular responses to proteotoxic and oxidative stresses. Taking advantage of the Drosophila system to investigate the biology of the Nrf protein family may thus contribute to the understanding of human diseases that are associated with cellular stress, possibly including N-glycanase deficiency. The second chapter of my thesis focuses on the relationship between high sugar diet, obesity and oxidative stress. It has been shown that obesity is associated with increased oxidative stress in multiple tissues. This increased oxidative stress can be caused by either increased ROS production or decreased antioxidant mechanisms. While it has been shown that overnutrition increases ROS production in mitochondria, how nutrition surplus affects antioxidant defense pathways is less well understood. I hypothesized that nutrition surplus compromises the oxidative stress defense. To explore this idea, I established an obesity model in which Drosophila is exposed to a high-sucrose diet. Consistent with the starting hypothesis, I found that high-sucrose food suppresses the fly’s oxidative stress defense. Further experiments are needed to understand the molecular mechanism by which high-sucrose diet reduces antioxidant responses. My experiments establish a connection between high-sucrose diet and oxidative stress defense and demonstrate the advantage of using the fruit fly as an animal model to study the health effects of obesity and related metabolic diseases.
Author: Mariarosaria Santillo Publisher: Frontiers Media SA ISBN: 2889457265 Category : Electronic books Languages : en Pages : 258
Book Description
The role of ROS/RNS signaling in cardiovascular functions and diseases is increasingly emerging in the last decades. The involvement of ROS/RNS in the control of a large number of cardiovascular functions like the regulation of the vascular tone, the control of blood pressure or myocyte excitation-contraction coupling and force development has been broadly investigated and in part clarified. On the other hand, many efforts have been focused in clarifying the redox mechanisms involved in cardiovascular diseases like ischemia/reperfusion injury, diabetes-associated cardiovascular dysfunctions, atherosclerosis or hypertension, just to mention the major ones. However, in most cases the two levels of investigation remain separate and not interlaced, failing in the attempt to provide a unified vision of the pathophysiologic mechanisms of cardiovascular diseases. The major aim of the Research Topic has been to collect original papers and review articles dealing with the issue from basic to translation research point of views. The topic includes contributions that highlight different interesting aspects of cardiovascular biology with an integrated approach useful for the development of new ideas and advancements in the field of redox signaling in the control of normal cardiovascular functions and their disruption in diseases.
Author: Walter Gottlieb Land Publisher: Springer ISBN: 3319786555 Category : Medical Languages : en Pages : 870
Book Description
This book presents current understanding of the importance of modern immunology in the etiopathogenesis of human diseases and explores how this understanding is impacting on diagnosis, prognosis, treatment, and prophylaxis. As the core of modern immunology, the “danger/injury model” is introduced and addressed throughout the book. Volume I of the book describes the network of damage-associated molecular pattern molecules (DAMPs) and examines the central role of DAMPs in cellular stress responses and associated regulated cell death, the promotion and resolution of inflammation, the activation of innate lymphoid cells and unconventional T cells, the stimulation of adaptive immunity, and tissue repair. The significance of DAMPs in a wide range of human diseases will then be explored in Volume II of the book, with discussion of the implications of injury-induced innate immunity for present and future treatments. This book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from immunity and inflammation research into clinical practice. The readership will include practitioners and clinicians such as hematologists, rheumatologists, traumatologists, oncologists, intensive care anesthetists, endocrinologists such as diabetologists, psychiatrists, neurologists, pharmacists, and transplantologists.
Author: Ruma Banerjee Publisher: John Wiley & Sons ISBN: 9780470177327 Category : Science Languages : en Pages : 350
Book Description
This is the premier, single-source reference on redox biochemistry, a rapidly emerging field. This reference presents the basic principles and includes detailed chapters focusing on various aspects of five primary areas of redox biochemistry: antioxidant molecules and redox cofactors; antioxidant enzymes; redox regulation of physiological processes; pathological processes related to redox; and specialized methods. This is a go-to resource for professionals in pharmaceuticals, medicine, immunology, nutrition, and environmental fields and an excellent text for upper-level students.
Author: Kevin Strange Publisher: Springer Science & Business Media ISBN: 1597451517 Category : Medical Languages : en Pages : 292
Book Description
Molecular biology has driven a powerful reductionist, or “molecule-c- tric,” approach to biological research in the last half of the 20th century. Red- tionism is the attempt to explain complex phenomena by defining the functional properties of the individual components of the system. Bloom (1) has referred to the post-genome sequencing era as the end of “naïve reductionism. ” Red- tionist methods will continue to be an essential element of all biological research efforts, but “naïve reductionism,” the belief that reductionism alone can lead to a complete understanding of living organisms, is not tenable. Organisms are clearly much more than the sum of their parts, and the behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. Systems biology has emerged in the wake of genome sequencing as the s- cessor to reductionism (2–5). The “systems” of systems biology are defined over a wide span of complexity ranging from two macromolecules that interact to carry out a specific task to whole organisms. Systems biology is integrative and seeks to understand and predict the behavior or “emergent” properties of complex, multicomponent biological processes. A systems-level characteri- tion of a biological process addresses the following three main questions: (1) What are the parts of the system (i. e.
Author: Publisher: Academic Press ISBN: 0080961371 Category : Science Languages : en Pages : 482
Book Description
This cutting-edge resource includes up-to-date information on zebrafish physiology and the tools used to study it, not only as a model species for studies of other vertebrates but with application for studies of human disease and aquatic toxicology. The utility of zebrafish for physiological research is based on several key features including i) a "fully" sequenced genome, ii) rapid (~3 month) generation times), iii) their capacity to produce large numbers of externally fertilized eggs, iv) optical transparency of embryos and larvae, and v) the applicability of reverse and forward genetics to assess gene function. Gene knockdown in embryos and the production of transgenic strains are now standard techniques being used to assess physiology. This book will be of keen interest not only to the typical readers of Fish Physiology but also to biomedical researchers, toxicologists and developmental biologists. Integrates and synthesizes the biology of the zebrafish under one cover Features contributions from the leading researchers in their fields Reaches a wider audience of researchers and biologists with its broad inclusion of subjects relating to zebrafish physiology
Author: Isabella Dalle-Donne Publisher: John Wiley & Sons ISBN: 0471973114 Category : Science Languages : en Pages : 978
Book Description
Methodology and applications of redox proteomics The relatively new and rapidly changing field of redox proteomics has the potential to revolutionize how we diagnose disease, assess risks, determine prognoses, and target therapeutic strategies for people with inflammatory and aging-associated diseases. This collection brings together, in one comprehensive volume, a broad array of information and insights into normal and altered physiology, molecular mechanisms of disease states, and new applications of the rapidly evolving techniques of proteomics. Written by some of the finest investigators in this area, Redox Proteomics: From Protein Modifications to Cellular Dysfunction and Diseases examines the key topics of redox proteomics and redox control of cellular function, including: * The role of oxidized proteins in various disorders * Pioneering studies on the development of redox proteomics * Analytical methodologies for identification and structural characterization of proteins affected by oxidative/nitrosative modifications * The response and regulation of protein oxidation in different cell types * The pathological implications of protein oxidation for conditions, including asthma, cardiovascular disease, diabetes, preeclampsia, and Alzheimer's disease Distinguished by its in-depth discussions, balanced methodological approach, and emphasis on medical applications and diagnosis development, Redox Proteomics is a rich resource for all professionals with an interest in proteomics, cellular physiology and its alterations in disease states, and related fields.
Author: Cheng Wang Publisher: John Wiley & Sons ISBN: 0470922745 Category : Science Languages : en Pages : 819
Book Description
This book describes how systems biology, pharmacogenomic and behavioral approaches, as applied to neurodevelopmental toxicology, provide a structure to arrange information in a biological model. Authors review and discuss approaches that can be used as effective tools to dissect mechanisms underlying pharmacological and toxicological phenomena associated with the exposure to drugs or environmental toxicants during development. This book presents cross-cutting research tools and animal models, along with applications to the studies associated with potential anesthetic-induced developmental neurotoxicity; the developmental basis of adolescent or adult onset of disease; risk assessment of methyl mercury and its effects on neurodevelopment; challenges in the field to identify environmental factors of relevance to autism; and the strategy and progress of epilepsy research.
Author: Vladimir V. Frolkis Publisher: CRC Press ISBN: 9780849367410 Category : Medical Languages : en Pages : 440
Book Description
This book presents results of lifespan prolongation studies obtained from experimental animal models and clinical and epidemiological human investigations. Modern theories, experimental models, and mathematical models of aging are described, as well as factors identified in lifespan prolongation, such as reduced body temperature, calorie- and protein-restricted diets, antioxidants, enterosorption, motor activity, modulators of genome expression, ionizing radiation, vitamins, microelements, and revitalizers. Gerontologists, physiologists, biochemists, and physicians active in the field of aging will find this book to be an interesting addition to their reference library.
Author: Donald L. Riddle Publisher: Firefly Books ISBN: 9780879695323 Category : Medical Languages : en Pages : 1252
Book Description
Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR