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Author: Raffaella Gozzelino Publisher: Frontiers Media SA ISBN: 2889195244 Category : Science (General) Languages : en Pages : 481
Book Description
The iron element (Fe) is strictly required for the survival of most forms of life, including bacteria, plants and humans. Fine-tuned regulatory mechanisms for Fe absorption, mobilization and recycling operate to maintain Fe homeostasis, the disruption of which leads to Fe overload or Fe depletion. Whereas the deleterious effect of Fe deficiency relies on reduced oxygen transport and diminished activity of Fe-dependent enzymes, the cytotoxicity induced by Fe overload is due to the ability of this metal to act as a pro-oxidant and catalyze the formation of highly reactive hydroxyl radicals via the Fenton chemistry. This results in unfettered oxidative stress generation that, by inducing protein, lipid and DNA oxidation, leads to Fe-mediated programmed cell death and organ dysfunction. Major and systemic Fe overloads occurring in hemochromatosis and Fe-loading anemias have been extensively studied. However, localized tissue Fe overload was recently associated to a variety of pathologies, such as infection, inflammation, cancer, cardiovascular and neurodegenerative disorders. In keeping with the existence of cross-regulatory interactions between Fe homeostasis and the pathophysiology of these diseases, further investigations on the mechanisms that provide cellular and systemic adaptation to tissue Fe overload are instrumental for future therapeutic approaches. Thus, we encourage our colleagues to submit original research papers, reviews, perspectives, methods and technology reports to contribute their findings to a current state of the art on a comprehensive overview of the importance of iron metabolism in pathophysiologic conditions.
Author: Raffaella Gozzelino Publisher: Frontiers Media SA ISBN: 2889195244 Category : Science (General) Languages : en Pages : 481
Book Description
The iron element (Fe) is strictly required for the survival of most forms of life, including bacteria, plants and humans. Fine-tuned regulatory mechanisms for Fe absorption, mobilization and recycling operate to maintain Fe homeostasis, the disruption of which leads to Fe overload or Fe depletion. Whereas the deleterious effect of Fe deficiency relies on reduced oxygen transport and diminished activity of Fe-dependent enzymes, the cytotoxicity induced by Fe overload is due to the ability of this metal to act as a pro-oxidant and catalyze the formation of highly reactive hydroxyl radicals via the Fenton chemistry. This results in unfettered oxidative stress generation that, by inducing protein, lipid and DNA oxidation, leads to Fe-mediated programmed cell death and organ dysfunction. Major and systemic Fe overloads occurring in hemochromatosis and Fe-loading anemias have been extensively studied. However, localized tissue Fe overload was recently associated to a variety of pathologies, such as infection, inflammation, cancer, cardiovascular and neurodegenerative disorders. In keeping with the existence of cross-regulatory interactions between Fe homeostasis and the pathophysiology of these diseases, further investigations on the mechanisms that provide cellular and systemic adaptation to tissue Fe overload are instrumental for future therapeutic approaches. Thus, we encourage our colleagues to submit original research papers, reviews, perspectives, methods and technology reports to contribute their findings to a current state of the art on a comprehensive overview of the importance of iron metabolism in pathophysiologic conditions.
Author: Gregory J. Anderson Publisher: Springer Science & Business Media ISBN: 1603274855 Category : Medical Languages : en Pages : 705
Book Description
Iron Physiology and Pathophysiology in Humans provides health professionals in many areas of research and practice with the most up-to-date and well-referenced volume on the importance of iron as a nutrient and its role in health and disease. This important new volume is the benchmark in the complex area of interrelationships between the essentiality of iron, its functions throughout the body, including its critical role in erythropoiesis, the biochemistry and clinical relevance of iron-containing enzymes and other molecules involved in iron absorption, transport and metabolism, he importance of optimal iron status on immune function, and links between iron and the liver, heart, brain and other organs. Moreover, the interactions between genetic and environmental factors and the numerous co-morbidities seen with both iron deficiency and iron overload in at risk populations are clearly delineated so that students as well as practitioners can better understand the complexities of these interactions. Key features of the volume include an in-depth index and recommendations and practice guidelines are included in relevant chapters. The volume contains more than 100 detailed tables and informative figures and up-to-date references that provide the reader with excellent sources of information about the critical role of iron nutrition, optimal iron status and the adverse clinical consequences of altered iron homeostasis. Iron Physiology and Pathophysiology in Humans is an excellent new text as well as the most authoritative resource in the field.
Author: Gregory J. Anderson Publisher: Humana Press ISBN: 9781493957651 Category : Medical Languages : en Pages : 704
Book Description
Iron Physiology and Pathophysiology in Humans provides health professionals in many areas of research and practice with the most up-to-date and well-referenced volume on the importance of iron as a nutrient and its role in health and disease. This important new volume is the benchmark in the complex area of interrelationships between the essentiality of iron, its functions throughout the body, including its critical role in erythropoiesis, the biochemistry and clinical relevance of iron-containing enzymes and other molecules involved in iron absorption, transport and metabolism, he importance of optimal iron status on immune function, and links between iron and the liver, heart, brain and other organs. Moreover, the interactions between genetic and environmental factors and the numerous co-morbidities seen with both iron deficiency and iron overload in at risk populations are clearly delineated so that students as well as practitioners can better understand the complexities of these interactions. Key features of the volume include an in-depth index and recommendations and practice guidelines are included in relevant chapters. The volume contains more than 100 detailed tables and informative figures and up-to-date references that provide the reader with excellent sources of information about the critical role of iron nutrition, optimal iron status and the adverse clinical consequences of altered iron homeostasis. Iron Physiology and Pathophysiology in Humans is an excellent new text as well as the most authoritative resource in the field.
Author: Vida Zhang Publisher: ISBN: Category : Languages : en Pages : 114
Book Description
Iron is an essential trace mineral for normal biological function, and systemic iron homeostasis is tightly regulated via complex systemic mechanisms and iron transporters. While there has been much focus on systemic iron regulation and homeostasis, iron regulation in the lung has not been well characterized. In addition, little is understood about the regulation of iron transporters and their role in specific cell types and under different pathophysiological conditions in the lung. Altered iron levels have also been associated with various lung pathologies, with iron overload associated with acute lung iron injury and idiopathic pulmonary fibrosis severity and iron deficiency correlating with worse pulmonary arterial hypertension (PAH). Our goals were to elucidate the effect of iron dysregulation in multiple lung pathologies and to further explore the role of iron transporters in the lung. For Chapters One and Two, we utilized hepcidin knockout mice (HKO) as a model of severe iron overload. In Chapter One, we induced acute lung injury (ALI) in HKO mice and wild-type (WT) littermates via oropharyngeal aspiration (OP) of lipopolysaccharide. While we did not observe any major differences in systemic inflammatory response or airway neutrophil infiltration, we did notice a mild and transient increase in vascular leakage and increased neutrophil activity, potentially due to increased lung tissue apoptosis. In Chapter Two, we treated HKO mice and WT littermates with bleomycin OP to induce pulmonary fibrosis and did not observe any effect of iron overload on lung collagen levels nor any differences in overall disease severity. Together, these data indicate that despite increased lung iron levels in human patients with ALI or idiopathic pulmonary fibrosis, iron overload may not play a significant role in the progression of either disease. In Chapter Three, we examined the role of ZIP8, a transmembrane divalent metal ion importer that is most highly expressed in the lung and inducible by inflammatory stimuli. We generated and characterized a novel global inducible ZIP8 knockout (KO) mouse and observed an unexpected phenotype of elevated spleen iron levels and decreased serum iron in ZIP8 KO mice. These data suggest that ZIP8 plays a role in iron recycling during homeostasis. However, we did not see any difference in response to the stress states of hemolytic anemia or iron deficiency in ZIP8 KO versus wild-type mice, suggesting that Zip8 may be redundant in this system. We also showed that ZIP8 is expressed on lung distal airspace epithelial cells and transports iron from the airway into lung tissue. ZIP8 deletion, however, had no detrimental effect on the severity of LPS-induced acute lung injury or on the outcomes of Klebsiella pneumoniae lung infection. Thus, ZIP8 plays a role in systemic iron homeostasis but does not modulate the severity of inflammatory lung injury or the host defense against a common bacterial cause of pneumonia. In Chapter Four, our goal was to establish a mouse model of iron deficiency in bone morphogenetic protein (BMP) type II receptor (Bmpr2)-associated PAH, as mutations in Bmpr2 are the most common genetic cause of PAH. We placed mice heterozygous for a Bmpr2-null allele and littermate controls on a low-iron diet to induce iron deficiency. Surprisingly, we found that iron-deficient Bmpr2 heterozygous mice may have less severe PAH than corresponding controls as evidenced by hemodynamics. We determined that while there are associations between iron deficiency and PAH potentially through Bmpr2, the Bmpr2 mutant mouse model is not the appropriate model for elucidating this relationship. Chapter Five explored the role of erythroferrone (ERFE) in a mouse model of b-thalassemia. ERFE is an erythroid hormone that increases iron availability by functioning as a BMP trap and inhibiting the master iron regulatory hormone hepcidin. Humans with b-thalassemia and other forms of ineffective erythropoiesis produce very high levels of ERFE. To define the contribution of excessive ERFE levels on the severity of b-thalassemia, we generated a "humanized" mouse model of b-thalassemia by crossing mice overexpressing ERFE with Th3/+ mice, a b-thalassemia mouse model that does not expresses high levels of ERFE. We found that elevated ERFE levels impair pup survival in a mouse model of b-thalassemia during early life and greatly increase iron loading in the context of ineffective erythropoiesis. These findings suggest that targeting ERFE in [Beta]-thalassemia should be further studied for potential therapeutic applications. In conclusion, we have examined the effect of iron overload and deficiency as well as the role of iron regulators and transporters on lung iron homeostasis and pathologies. Using various mouse models, we have characterized the effects of iron during ALI, pulmonary fibrosis and pulmonary vascular disease, the role of ZIP8 in iron pathophysiology, and the role of ERFE in [Beta]-thalassemia
Author: Patarabutr Masaratana Publisher: ISBN: Category : Iron Languages : en Pages : 660
Book Description
Hepcidin, the iron regulatory peptide, has been shown to inhibit iron absorption and reticuloendothelial iron recycling. Hereditary haemochromatosis is genetic iron overload disorders mostly caused by mutations of genes encoding hepcidin or iron sensing molecules. The studies in this thesis were conducted to further delineate the pathophysiology of iron loading and explore therapeutic options for such conditions. -- Hepcidin deficiency results in systemic iron overload as evidenced through the two mouse models used in the current study, hypotransferrinaemic (hpx/hpx) and hepcidinI knockout (HepcI-/-) mice. Hepcidin injection caused hypoferraemia in wild type mice, but not HepcI-/- mice. However, the treatment inhibited iron absorption, especially the uptake step, in the knockout. Hepcidin administration was also associated with decreased expression of the iron exporter, ferroportin, preferentially in the spleen. Despite a crucial role of hepcidin in iron loading, its application as therapeutic modality requires further investigation as differential response was found between normal and hepcidin-deficient mice. -- Another important contributor of haemochromatosis is tissue uptake of nontransferrin-bound iron (NTBI). A few NTBI transporters have been identified including L-type voltage dependent calcium channels (LVDCCs) and a zinc transporter, Zip14. The interference of these NTBI transporters to modulate iron loading was therefore explored. The administration of verapamil, a LVDCC blocker, was associated with a global reduction in tissue iron levels in hpx/hpx, but not HepcI-/- mice. This was achieved through a yet unclarified mechanism. In contrast, dietary supplementation of zinc in HepcI-/- mice resulted in reduced iron accumulation specifically in the liver.
Author: Chaim Hershko Publisher: Springer Science & Business Media ISBN: 1461505933 Category : Science Languages : en Pages : 275
Book Description
Within the last few years, iron research has yielded exciting new insights into the under standing of normal iron homeostasis. However, normal iron physiology offers little protec tion from the toxic effects of pathological iron accumulation, because nature did not equip us with effective mechanisms of iron excretion. Excess iron may be effectively removed by phlebotomy in hereditary hemochromatosis, but this method cannot be applied to chronic anemias associated with iron overload. In these diseases, iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Iron chelating therapy has changed the quality of life and life expectancy of thalassemic patients. However, the high cost and rigorous requirements of deferoxamine therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Such development, and the evolution of improved strategies of iron chelating therapy require better understanding of the pathophysiology of iron toxicity and the mechanism of action of iron chelating drugs. The timeliness of the present volume is underlined by several significant develop ments in recent years. New insights have been gained into the molecular basis of aberrant iron handling in hereditary disorders and the pathophysiology of iron overload (Chapters 1-5).
Author: James C. Barton Publisher: Cambridge University Press ISBN: 9780521593809 Category : Medical Languages : en Pages : 622
Book Description
Once considered a rare condition, hemochromatosis is now acknowledged as one of the commonest inherited disorders, affecting one in two hundred people of Western Caucasian descent and in the U.S. alone, over one million people. This is the most comprehensive clinical reference yet on hemochromatosis. The international team of 94 authors from twelve countries includes specialists in internal medicine, hematology, hepatology, genetics, biochemistry, and molecular biology. In 57 in-depth chapters they cover all aspects of pathophysiology, epidemiology, diagnosis and treatment. The text thoroughly explains the latest developments in the genetics of the disorder, including sections on screening, diagnostic techniques, and clinical complications. In addition, chapters consider social and ethical issues. With over 200 illustrations--including 40 color plates--this is today's definitive resource for all clinicians involved in the management of hemochromatosis, and for scientists interested in iron metabolism and iron overload.
Author: Robert Provenzano Publisher: Springer ISBN: 1493973606 Category : Medical Languages : en Pages : 248
Book Description
This concise and practical resource brings together recent advances in identifying and managing anemia of chronic disease (inflammation), genetically related anemia and anemia related to chronic end organ damage. Chapters provide a detailed analysis of the current science of anemia, approaches to different patient populations, comorbid conditions and nutritional aspects of anemia. Novel therapies focused on physiological pathways are introduced and discussed. Controversies from the perspective of subspecialists focused in treating major causes of anemia within their specific disciplines are also presented. Easy-to-reference and authored by experts in each clinical scenario, Management of Anemia is the launching point for learning more about this challenging and common condition.
Author: Susu M Zughaier Publisher: Frontiers Media SA ISBN: 2889456625 Category : Languages : en Pages : 156
Book Description
The collection of articles published in this eBook represent different facets of the interactions between pathogens and their host concerning the battle for iron. Pathogens have developed different strategies to acquire iron from their host. These include the production of siderophores, heme acquisition and ferrous iron uptake.
Author: Raffaella Gozzelino
Author: Raffaella Gozzelino
Author: Gregory J. Anderson
Author: Gregory J. Anderson
Author: Vida Zhang
Author: Virgil F. Fairbanks
Author: Patarabutr Masaratana
Author: Chaim Hershko
Author: James C. Barton
Author: Robert Provenzano
Author: Susu M Zughaier