[PDF] Zinc Deficiency Induces Apoptosis Via Mitochondrial P53 And Caspase Dependent Pathways In Human Neuronal Precursor Cells eBook

Author : Rohit Seth
Publisher :
Page : 8 pages
File Size : 29,98 MB
Release : 2015
Category :
ISBN :

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Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin-æ, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency.

Author : Rikki Somers Corniola
Publisher :
Page : 64 pages
File Size : 50,3 MB
Release : 2010
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ABSTRACT: Although zinc has been implicated in the functionality of the hippocampus since the 1970's, the recent discovery of adult neuronal stem cells in this region of the brain provides the potential for novel zinc-regulated hippocampal processes. The current work addressed the role of zinc in the proliferation, maintenance, and survival of neuronal precursor cells. First, this work employed a genome-wide analysis of the effect of dietary zinc deficiency in the hippocampus. The data revealed that 3 weeks of dietary zinc deficiency resulted in the down-regulation of nearly 400 genes, many of which were associated with synaptic plasticity (stau2, syn1), neurotransmitter receptors (grin1, gabrb3), neurogenesis (iguana, id2, nek9), and cell viability (sod2, stat3). Furthermore, using a candidate gene approach, the current work shows a vital role of zinc in p53-mediated mechanisms governing proliferation and apoptosis of neuronal precursor cells. For example, zinc deficient cells show increased nuclear and mitochondrial translocation of the tumor suppressor p53. Using a dominant negative construct to ensure p53 regulation, this work shows that nuclear p53 is responsible for the downstream target genes responsible for cell cycle arrest (reprimo, lats2). These data coincide with a decrease in BrdU-labeling. The current work also highlights initial protective responses governed by the transcription factor p53. However, zinc deficient neuronal precursors also show a p53-dependent increase in mitochondrial reactive oxygen species which could be mediated by a decreased expression of glutathione peroxidase mRNA and mitochondrial localized p53. If the deficiency is severe or prolonged nuclear p53 regulates expression of apoptotic genes (rb1, tgf-â) whereas, mitochondrial p53 mediates interactions with Bcl-family proteins to initiate a loss in mitochondrial membrane potential. Ultimately, the current work adds to the essential role of zinc in the hippocampus and identifies a novel mechanism for zinc in the regulation of neuronal precursor proliferation, maintenance, and survival.

Author : Toshiyuki Fukada
Publisher : MDPI
Page : 293 pages
File Size : 37,51 MB
Release : 2018-05-04
Category : Science
ISBN : 3038428213

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This book is a printed edition of the Special Issue "Zinc Signaling in Physiology and Pathogenesis" that was published in IJMS

Author : Yashwant V. Pathak
Publisher : CRC Press
Page : 568 pages
File Size : 33,73 MB
Release : 2017-09-29
Category : Technology & Engineering
ISBN : 1498765122

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Genomics and related areas of research have contributed greatly to the understanding of the cellular and molecular mechanisms underlying diet–disease relationships. In the past decade, the evidence has become stronger for a direct link between genome/epigenome damage and increased risk for adverse health outcomes. It is now exceedingly clear that micronutrients are critical as cofactors for many cellular functions, including DNA repair enzymes, methylation of CpG sequences, DNA oxidation, and/or uracil incorporation into DNA. Nutrigenomics and Nutraceuticals: Clinical Relevance and Disease Prevention brings new perspectives on disease prevention strategy based on the genomic knowledge and nutraceuticals of an individual and the diet he or she receives. This book discusses the integration and application of genetic and genomics technology into nutrition research and paves the way for the development of nutrition research programs that are aimed at the prevention and control of chronic disease through genomics-based nutritional interventions. In this book, the editors bring together a wide spectrum of nutritional scientists worldwide to contribute to the growing knowledge in the field of nutrigenomics and nutraceuticals.

Author : Marcos Roberto de Oliveira
Publisher : Elsevier
Page : 800 pages
File Size : 13,14 MB
Release : 2022-11-30
Category : Science
ISBN : 0323884636

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Mitochondrial Intoxication explores the effects toxic molecules can have upon mitochondrial physiology in the human body. Each chapter is dedicated to a specific toxicant, including pollutants, food additives, illicit and pharmaceutical drugs, and heavy metals. This book considers the implications and impact these have upon mitochondria and the diseases that can result from dysfunction and impairment in the human body. Furthermore, the book provides an overview of mitochondrial physiology and assesses the advances and challenges in testing mitochondrial toxicity. Case studies exploring mitochondrial intoxication in pregnancy and in the geriatric population are also included. This is a comprehensive reference on the main toxicants impacting mitochondria in the human body, and the consequences this can have for health and disease. Features a wide range of toxicants and their effects on mitochondrial physiology Covers molecular markers of mitochondrial intoxication Includes case studies that illustrate the health impacts of toxicity upon mitochondria Considers future directions regarding the study of mitochondrial intoxication

Author : Andreas Grabrucker
Publisher : Academic Press
Page : 224 pages
File Size : 20,95 MB
Release : 2020-07-08
Category : Psychology
ISBN : 0128211334

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Biometals in Autism Spectrum Disorders focuses on trace metals and autism. Compared to other references examining ASDs or metallomics, this book presents findings of abnormal metal homeostasis in ASD, providing an overview of current findings on trace metal biology, its role in ASD etiology, and how abnormal trace metal biology may be a common factor of several genetic and non-genetic causes of ASDs that were once considered unrelated. This comprehensive resource opens new vistas for the development of new therapies based on the targeted manipulation of trace metal homeostasis that will generate new awareness surrounding trace metal levels during pregnancy. Reviews the role of trace metals in brain development Summarizes research linking trace metals and autism Explores heterogenous phenotypes as a factor of genetic and non-genetic factors Includes animal and human stem research Contains many useful diagrams, tables and flow charts Proposes future therapies based on biometal homeostasis

Author : Atta-ur-Rahman
Publisher : Bentham Science Publishers
Page : 272 pages
File Size : 13,96 MB
Release : 2015-11-27
Category : Science
ISBN : 1681081474

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Frontiers in Clinical Drug Research - Alzheimer Disorders is an e-Book series concerned with Alzheimer's disease (AD) that causes dementia, or loss of brain function. The disease affects the parts of the brain that deal with memory, thought, and language. Chapters in each volume focus on (Alzheimer Disorders) drug research with special emphasis on clinical trials, research on drugs in advanced stages of development and cure for Alzheimer’s disease and related disorders. Frontiers in Clinical Drug Research - Alzheimer Disorders will be of particular interest to readers interested in drug therapy of this specific neurodegenerative condition and related brain disorders as the series provides relevant reviews written by experts in field of Alzheimer’s Disease research. The fourth volume of this series features research on - Melatoninergic Pathways in Alzheimer's disease, - Nutritional Approaches in Alzheimer’s disease prevention, - Updates on drugs and strategies for Alzheimer’s disease prevention

Author : Wael Mohamed
Publisher : Springer Nature
Page : 313 pages
File Size : 44,13 MB
Release : 2022-03-29
Category : Medical
ISBN : 9811664676

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This book comprehensively reviews the relationship between micronutrients and brain in health and diseases. It explains the relationship between micronutrients and brain functions, neurogenesis, and cognitive functions. The book also explores the relationship between micronutrients and brain disorders including depression, epilepsy, PD, and Autism. It further explores the recent advancements in understanding the important role of micronutrients as therapeutics in various brain disorders like TBI and AD. Lastly, it presents an overview of micronutrients as neuroprotective agents along with the main principles of nutrigenomics.

Author : Colin R Martin
Publisher : Elsevier
Page : 816 pages
File Size : 40,99 MB
Release : 2023-06-06
Category : Medical
ISBN : 0323915728

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Vitamins and Minerals in Neurological Disorders offers readers a comprehensive reference addressing their relationship to brain health in a wide variety of neurological diseases. Examining various compounds, this broad coverage allows readers to learn about the role nutrient deficiency plays in the pathology of many conditions, as well as their potential in treatment. The book covers diseases including Alzheimer’s, Parkinson’s, ALS, and MS, along with severe neurological conditions like brain injury, stroke, headache and migraine. This volume provides a platform for research on vitamins, minerals and future investigations of these compounds. Summarizes vitamin and mineral research for a variety of neurological conditions Contains chapter abstracts, key facts, a dictionary and a summary Covers nutraceutical and botanical use in Alzheimer’s, Parkinson’s, ALS, MS, and more Includes conditions like migraine, headache, stroke and brain injury

Author : Jennifer Guadagno
Publisher :
Page : pages
File Size : 44,78 MB
Release : 2015
Category :
ISBN :

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The persistence of neural precursor cells (NPCs) in distinct niches of the adult brain and spinal cord provides an important opportunity for regeneration in the affected nervous system. In the adult brain, neural precursor cells (NPCs) generate new neurons that can be integrated into the CNS circuitry to replace damaged or lost neurons, and contribute to learning and memory processes. Deregulated neurogenesis has been observed under both acute and chronic neurological conditions including stroke, Alzheimer's disease, and Parkinson's disease. The extent to which neurogenesis contributes to brain repair is severely limited by the neuroinflammatory processes associated with these neurodegenerative conditions. During injury, microglia, the CNS resident immune cells become activated and produce a number of anti- and pro-inflammatory factors that can modulate neurogenesis and survival of NPCs. The goal of this study was to identify mechanisms of NPC apoptosis induced by microglia-derived cytokines. Using a conditioned media model, we have identified that activation of the TNF?, IL-1? and Fas signaling pathways induces death of NPCs via the intrinsic pathway of apoptosis in vitro. TNF? activates Puma and NPC apoptosis via an NF-?B-dependent mechanism. Activation of the IL-1? pathway, by microglia-derived or rIL-1? induces cell cycle arrest and apoptosis via p53-dependent upregulation of p21 and Puma. IL-1? can also induce an increased expression of Fas via an NF-?B-dependent pathway. Fas signaling in NPCs also culminates in activation of Puma and induction of mitochondrial-dependent apoptosis of NPCs. Puma appears to be a dominant regulator of cytokine-induced NPC apoptosis in vitro, as well as in an in vivo model of spinal cord injury. This study implicates microglia-derived TNF? and IL-1? as potent inducers of the BH3-only protein Puma through activation of the NF-?B and p53 pathways, respectively. Furthermore, these findings provide novel molecular targets to improve the survival of both endogenous and transplanted NPCs in regenerative therapies for acute and chronic neurological conditions.