scholarly journals General Aspects of Metal Ions as Signaling Agents in Health and Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1417 ◽  
Author(s):  
Karolina Krzywoszyńska ◽  
Danuta Witkowska ◽  
Jolanta Świątek-Kozłowska ◽  
Agnieszka Szebesczyk ◽  
Henryk Kozłowski
Keyword(s):  
Signal Transduction ◽  
Metal Ions ◽  
Metal Ion ◽  
Current Knowledge ◽  
Calcium Dependent ◽  
Pathological Conditions ◽  
Dependent Signal ◽  
Health And Disease ◽  
General Aspects ◽  
Cellular Zinc

This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also involved in a recently discovered type of programmed cell death, ferroptosis. The important differences in metal ion signaling, and its disease-leading alterations, are also discussed.

Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma–associated herpesvirus

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2374-2380 ◽  
Author(s):  
J. Paul Zoeteweij ◽  
Ashlee V. Moses ◽  
Andrea S. Rinderknecht ◽  
David A. Davis ◽  
Willem W. Overwijk ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Intracellular Signaling ◽  
Primary Effusion Lymphoma ◽  
Single Cells ◽  
Kaposi Sarcoma ◽  
Lytic Cycle ◽  
Virus Reactivation ◽  
Calcium Dependent ◽  
Latently Infected ◽  
Dependent Signal

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants. Agents that mobilized intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production. Calcium-mediated virus reactivation was blocked by specific inhibitors of calcineurin-dependent signal transduction (cyclosporine, FK506). Similarly, calcium-mediated virus reactivation in KSHV-infected dermal microvascular endothelial cells was blocked by cyclosporine. Furthermore, retroviral transduction with plasmid DNA encoding VIVIT, a peptide specifically blocking calcineurin-NFAT interactions, inhibited calcium-dependent KSHV reactivation. By contrast, chemical induction of lytic-phase infection by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate was blocked by protein kinase C inhibitors, but not by calcineurin inhibitors. In summary, calcineurin-dependent signal transduction, an important signaling cascade in vivo, induces calcium-dependent KSHV replication, providing a possible target for the design of antiherpesvirus strategies in KSHV-infected patients.

scholarly journals The endocannabinoid pathway and the female reproductive organs

2012 ◽  
Vol 50 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Anna Maria Di Blasio ◽  
Michele Vignali ◽  
Davide Gentilini
Keyword(s):  
Signal Transduction ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Reproductive Organs ◽  
Signal Transduction Pathways ◽  
Peroxisome Proliferator ◽  
Pathological Conditions ◽  
Peroxisome Proliferator Activated Receptors ◽  
Synthesis And Degradation ◽  
Female Reproductive Organs

Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.

scholarly journals Regulation of CAR and PXR Expression in Health and Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2395
Author(s):  
Martine Daujat-Chavanieu ◽  
Sabine Gerbal-Chaloin
Keyword(s):  
Transcription Factors ◽  
Nuclear Receptor ◽  
Current Knowledge ◽  
Constitutive Androstane Receptor ◽  
Adult Life ◽  
Pregnane X Receptor ◽  
Regulatory Mechanisms ◽  
Nuclear Receptor Superfamily ◽  
Pathological Conditions ◽  
Health And Disease

Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are members of the nuclear receptor superfamily that mainly act as ligand-activated transcription factors. Their functions have long been associated with the regulation of drug metabolism and disposition, and it is now well established that they are implicated in physiological and pathological conditions. Considerable efforts have been made to understand the regulation of their activity by their cognate ligand; however, additional regulatory mechanisms, among which the regulation of their expression, modulate their pleiotropic effects. This review summarizes the current knowledge on CAR and PXR expression during development and adult life; tissue distribution; spatial, temporal, and metabolic regulations; as well as in pathological situations, including chronic diseases and cancers. The expression of CAR and PXR is modulated by complex regulatory mechanisms that involve the interplay of transcription factors and also post-transcriptional and epigenetic modifications. Moreover, many environmental stimuli affect CAR and PXR expression through mechanisms that have not been elucidated.

scholarly journals Structural basis of Sorcin-mediated calcium-dependent signal transduction

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Andrea Ilari ◽  
Annarita Fiorillo ◽  
Elena Poser ◽  
Vasiliki S. Lalioti ◽  
Gustav N. Sundell ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Structural Basis ◽  
Calcium Dependent ◽  
Dependent Signal

scholarly journals Glia-Derived Extracellular Vesicles: Role in Central Nervous System Communication in Health and Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Cristiana Pistono ◽  
Nea Bister ◽  
Iveta Stanová ◽  
Tarja Malm
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Glial Cells ◽  
Current Knowledge ◽  
Physiological State ◽  
General Term ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Health And Disease

Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.

scholarly journals Metal ions suppress the abnormal taste behavior of the Drosophila mutant malvolio.

1998 ◽  
Vol 201 (1) ◽  
pp. 115-120
Author(s):  
S Orgad ◽  
H Nelson ◽  
D Segal ◽  
N Nelson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Metal Ions ◽  
Metal Ion ◽  
Adult Stage ◽  
Taste Perception ◽  
Natural Resistance ◽  
Ion Transporters ◽  
Normal Taste ◽  
Drosophila Mutant

A mutation in the malvolio (mvl) gene affects taste behavior in Drosophila melanogaster. The malvolio gene encodes a protein (MVL) that exhibits homology to the mammalian natural resistance-associated macrophage proteins. It is also homologous to the Smf1 protein from Saccharomyces cerevisiae, which we have recently demonstrated to function as a Mn2+/Zn2+ transporter. We proposed that the Drosophila and mammalian proteins, like the yeast SMF1 gene product, are metal-ion transporters. To test this hypothesis, malvolio mutant flies were allowed to develop, from egg to adulthood, on a medium containing elevated concentrations of metal ions. Mutant flies that were reared in the presence of 10 mmol l-1 MnCl2 or FeCl2 developed into adults with recovered taste behavior. CaCl2 or MgCl2 had no effect on the mutant's taste perception. ZnCl2 inhibited the effect of MnCl2 when both ions were supplied together. Similar suppression of the abnormal taste behavior was observed when mvl mutants were fed MnCl2 or FeCl2 only at the adult stage. Furthermore, exposure of adult mutant flies to these ions in the testing plate for only 2 h was sufficient to restore normal taste behavior. The suppression of the defective taste behavior suggests that MVL functions as a Mn2+/Fe2+ transporter and that Mn2+ and/or Fe2+ are involved in the signal transduction of taste perception in Drosophila adults.

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