scholarly journals Molecular regulation of copper excretion in the liver

2004 ◽  
Vol 63 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Cisca Wijmenga ◽  
Leo W. J. Klomp
Keyword(s):  
Wilson Disease ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
The Body ◽  
Genomic Tools ◽  
Essential Nutrient ◽  
Human Disorder ◽  
Cu Homeostasis ◽  
P Type ◽  
Pleiotropic Function

Cu is an essential nutrient that is required for a broad range of cellular and molecular processes. Mammals have efficient systems to control Cu homeostasis that operate at the level of controlling uptake, distribution, sequestration and excretion of Cu. The study of diseases associated with disturbed Cu homeostasis has greatly enhanced our understanding of the molecular mechanisms involved in Cu metabolism. In man the liver is responsible for excreting excess Cu from the body by means of biliary secretion. Wilson disease is a severe human disorder characterized by Cu accumulation in the liver as a result of a deficiency in biliary Cu secretion. This disorder is caused by mutations in the gene that encodes a Cu-transporting P-type ATPase (ATP7B). The MURR1 gene was identified recently, and it was hypothesized that this gene is also essential for biliary Cu excretion and is presumed to act downstream of ATP7B. MURR1 is mutated in canine Cu toxicosis, a disorder with phenotypic characteristics similar to those of Wilson disease. MURR1 encodes a protein that is of unknown function and is without detectable sequence homology to known proteins. MURR1 is readily detected in all tissues and cell types, suggesting that it may exhibit a pleiotropic function in different organs, which may or may not be exclusively linked to Cu homeostasis. The use of genetic, biochemical and genomic tools, as well as the development of appropriate models in organisms other than dog, will allow the elucidation of the molecular and cellular function of MURR1 in relation to hepatic Cu homeostasis and biliary Cu excretion.

scholarly journals The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis

2020 ◽  
Vol 21 (9) ◽  
pp. 3304
Author(s):  
James W.W. Winslow ◽  
Kirsten H. Limesand ◽  
Ningning Zhao
Keyword(s):  
Antioxidant Defense ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
The Body ◽  
Metal Transporters ◽  
Cellular Processes ◽  
The Past ◽  
Genes Encoding ◽  
Essential Nutrient

As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.

scholarly journals Antheridial development in the moss Physcomitrella patens : implications for understanding stem cells in mosses

2017 ◽  
Vol 373 (1739) ◽  
pp. 20160494 ◽  
Author(s):  
Rumiko Kofuji ◽  
Yasushi Yagita ◽  
Takashi Murata ◽  
Mitsuyasu Hasebe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Molecular Mechanisms ◽  
Physcomitrella Patens ◽  
Evolutionary Relationship ◽  
Terrestrial Ecosystem ◽  
Cell Types ◽  
Land Plant ◽  
The Body ◽  
New Type

Stem cells self-renew and produce precursor cells that differentiate to become specialized cell types. Land plants generate several types of stem cells that give rise to most organs of the plant body and whose characters determine the body organization. The moss Physcomitrella patens forms eight types of stem cells throughout its life cycle. Under gametangium-inducing conditions, multiple antheridium apical stem cells are formed at the tip of the gametophore and each antheridium apical stem cell divides to form an antheridium. We found that the gametophore apical stem cell, which typically forms leaf and stem tissues, changes to become a new type of stem cell, which we term the antheridium initial stem cell. This antheridium initial stem cell produces multiple antheridium apical stem cells, resulting in a cluster of antheridia at the tip of gametophore. This is the first report of a land plant stem cell directly producing another type of stem cell during normal development. Notably, the antheridium apical stem cells are distally produced from the antheridium initial stem cell, similar to the root cap stem cells of vascular plants, suggesting the use of similar molecular mechanisms and a possible evolutionary relationship. This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.

scholarly journals Molecular Aspects of Regeneration Mechanisms in Holothurians

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 250 ◽  
Author(s):  
Igor Yu. Dolmatov
Keyword(s):  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Molecular Data ◽  
The Body ◽  
Matrix Remodeling ◽  
Oxygen Species ◽  
Morphological And Molecular Data ◽  
Molecular Aspects ◽  
Different Cell Types

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation).

scholarly journals Circadian Regulation in Tissue Regeneration

2019 ◽  
Vol 20 (9) ◽  
pp. 2263 ◽  
Author(s):  
Ellen Paatela ◽  
Dane Munson ◽  
Nobuaki Kikyo
Keyword(s):  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
The Body ◽  
Circadian Regulation ◽  
Global Regulator ◽  
Protein Coding ◽  
Translational Activity ◽  
Regenerative Therapies ◽  
Regulation Of Regeneration

Circadian rhythms regulate over 40% of protein-coding genes in at least one organ in the body through mechanisms tied to the central circadian clock and to cell-intrinsic auto-regulatory feedback loops. Distinct diurnal differences in regulation of regeneration have been found in several organs, including skin, intestinal, and hematopoietic systems. Each regenerating system contains a complex network of cell types with different circadian mechanisms contributing to regeneration. In this review, we elucidate circadian regeneration mechanisms in the three representative systems. We also suggest circadian regulation of global translational activity as an understudied global regulator of regenerative capacity. A more detailed understanding of the molecular mechanisms underlying circadian regulation of tissue regeneration would accelerate the development of new regenerative therapies.

scholarly journals Dual binding capacity of mucosal immunoblasts to mucosal and synovial endothelium in humans: dissection of the molecular mechanisms.

1995 ◽  
Vol 181 (1) ◽  
pp. 137-149 ◽  
Author(s):  
M Salmi ◽  
D P Andrew ◽  
E C Butcher ◽  
S Jalkanen
Keyword(s):  
Molecular Mechanisms ◽  
Binding Capacity ◽  
Critical Role ◽  
Cell Types ◽  
The Body ◽  
Minor Role ◽  
Lymphocyte Function ◽  
High Endothelial Venules ◽  
Lamina Propria Lymphocyte ◽  
The Impact

Lymphocytes continuously migrate throughout the body in search of antigens. Virgin lymphocytes recirculate freely between the blood and different lymphatic organs, whereas immunoblasts extravasate preferentially into sites similar to those where they initially responded to antigen. Tissue-specific extravasation of lymphocytes is largely controlled by distinct lymphocyte surface receptors that mediate lymphocyte binding to high endothelial venules (HEV). In the present study, the molecular mechanisms determining the specificity of human mucosal (lamina propria) lymphocyte binding to different endothelial recognition systems were analyzed. Mucosal immunoblasts adhered five times better than small mucosal lymphocytes to mucosal HEV. Importantly, mucosal immunoblasts also bound to synovial HEV almost as efficiently as to mucosal HEV, but they did not adhere to peripheral lymph node HEV. To study the impact of different homing-associated molecules in this dual endothelial binding, we used a gut-derived T cell line and freshly isolated mucosal immunoblasts. Both cell types expressed integrins alpha 4, beta 1, beta 7, and lymphocyte function associated antigen 1 (LFA-1), and were CD44 positive, but practically L-selectin negative. Binding of mucosal immunoblasts to mucosal HEV was almost completely abolished by pretreatment with anti-beta 7 monoclonal antibodies, but it was independent of alpha 4/beta 1 function. In contrast, alpha 4/beta 1 partially mediated immunoblast adherence to synovial HEV, whereas alpha 4/beta 7 had only a minor role in adherence of blasts at this site. CD44 and LFA-1 contributed to HEV-binding both in mucosa and synovium. Taken together, this is the first report that demonstrates a critical role for alpha 4/beta 7 in the binding of gut lymphocytes to mucosal venules in humans. Moreover, a hitherto unknown interaction between mucosal effector cells and synovial endothelial cells was shown to be only partially mediated by the currently known homing receptors. The dual endothelial binding capacity of mucosal blasts may help to explain the pathogenesis of reactive arthritis not uncommonly associated with inflammatory and infectious bowel disease.

scholarly journals Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1314
Author(s):  
Tao Tong ◽  
Yanan Wang ◽  
Seong-Gook Kang ◽  
Kunlun Huang
Keyword(s):  
Molecular Mechanisms ◽  
Germ Line ◽  
Odorant Receptor ◽  
Cell Types ◽  
The Body ◽  
Flavor Compounds ◽  
Hepatic Lipid Accumulation ◽  
Serotonin Secretion ◽  
Or Gene ◽  
Or Genes

Prompted by the ground-breaking discovery of the rodent odorant receptor (OR) gene family within the olfactory epithelium nearly 30 years ago, followed by that of OR genes in cells of the mammalian germ line, and potentiated by the identification of ORs throughout the body, our appreciation for ORs as general chemoreceptors responding to odorant compounds in the regulation of physiological or pathophysiological processes continues to expand. Ectopic ORs are now activated by a diversity of flavor compounds and are involved in diverse physiological phenomena varying from adipogenesis to myogenesis to hepatic lipid accumulation to serotonin secretion. In this review, we outline the key biological functions of the ectopic ORs responding to flavor compounds and the underlying molecular mechanisms. We also discuss research opportunities for utilizing ectopic ORs as therapeutic strategies in the treatment of human disease as well as challenges to be overcome in the future. The recognition of the potent function, signaling pathway, and pharmacology of ectopic ORs in diverse tissues and cell types, coupled with the fact that they belong to G protein-coupled receptors, a highly druggable protein family, unequivocally highlight the potential of ectopic ORs responding to flavor compounds, especially food-derived odorant compounds, as a promising therapeutic strategy for various diseases.

scholarly journals A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Visweswara Rao Pasupuleti ◽  
Chandra Sekhar Arigela ◽  
Siew Hua Gan ◽  
Sirajudeen Kuttulebbai Nainamohamed Salam ◽  
Kumara Thevan Krishnan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Antioxidant Response ◽  
Dietary Factors ◽  
The Body ◽  
Related Factor ◽  
Antidiabetic Agent ◽  
Antioxidant Response Elements

Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world’s most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights.

scholarly journals Keith R. Porter Lecture, 1996. Of mice and men: genetic disorders of the cytoskeleton.

1997 ◽  
Vol 8 (2) ◽  
pp. 189-203 ◽  
Author(s):  
E Fuchs
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Disorders ◽  
Cell Types ◽  
The Body ◽  
Epidermal Keratinocytes ◽  
Massachusetts Institute Of Technology ◽  
Degenerative Diseases ◽  
Institute Of Technology ◽  
The University ◽  
Filament Network

Since the time when I was a postdoctoral fellow under the supervision of Dr. Howard Green, then at the Massachusetts Institute of Technology, I have been interested in understanding the molecular mechanisms underlying growth, differentiation, and development in the mammalian ectoderm. The ectoderm gives rise to epidermal keratinocytes and to neurons, which are the only two cell types of the body that devote most of their protein-synthesizing machinery to developing an elaborate cytoskeletal architecture composed of 10-nm intermediate filaments (IFs). Our interest is in understanding the architecture of the cytoskeleton in keratinocytes and in neurons, and in elucidating how perturbations in this architecture can lead to degenerative diseases of the skin and the nervous system. I will concentrate on the intermediate filament network of the skin and its associated genetic disorders, since this has been a long-standing interest of my laboratory at the University of Chicago.

scholarly journals Vascular Homeostasis and Inflammation in Health and Disease—Lessons from Single Cell Technologies

2020 ◽  
Vol 21 (13) ◽  
pp. 4688 ◽  
Author(s):  
Olga Bondareva ◽  
Bilal N. Sheikh
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Vascular System ◽  
Vascular Dysfunction ◽  
Rapid Development ◽  
Cell Types ◽  
The Body ◽  
Vascular Cells ◽  
Cell Technologies

The vascular system is critical infrastructure that transports oxygen and nutrients around the body, and dynamically adapts its function to an array of environmental changes. To fulfil the demands of diverse organs, each with unique functions and requirements, the vascular system displays vast regional heterogeneity as well as specialized cell types. Our understanding of the heterogeneity of vascular cells and the molecular mechanisms that regulate their function is beginning to benefit greatly from the rapid development of single cell technologies. Recent studies have started to analyze and map vascular beds in a range of organs in healthy and diseased states at single cell resolution. The current review focuses on recent biological insights on the vascular system garnered from single cell analyses. We cover the themes of vascular heterogeneity, phenotypic plasticity of vascular cells in pathologies such as atherosclerosis and cardiovascular disease, as well as the contribution of defective microvasculature to the development of neurodegenerative disorders such as Alzheimer’s disease. Further adaptation of single cell technologies to study the vascular system will be pivotal in uncovering the mechanisms that drive the array of diseases underpinned by vascular dysfunction.

Toxicology

2017 ◽  
Author(s):  
Robert Laumbach ◽  
Michael Gochfeld
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Toxicity Testing ◽  
The Body ◽  
Toxic Substances ◽  
Basic Principles ◽  
Practical Applications ◽  
Mechanisms Of Toxicity ◽  
Body Distribution ◽  
Threshold Doses

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.

Sign in / Sign up

Export Citation Format

Share Document