scholarly journals Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mohamed Ariff Iqbal ◽  
Eftekhar Eftekharpour
Keyword(s):  
Cell Fate ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Human Life ◽  
Redox Balance ◽  
Mammalian Brain ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Cellular Turnover

In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS) reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS) in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

scholarly journals Neuronal Activity-Dependent Control of Postnatal Neurogenesis and Gliogenesis

2018 ◽  
Vol 41 (1) ◽  
pp. 139-161 ◽  
Author(s):  
Ragnhildur T. Káradóttir ◽  
Chay T. Kuo
Keyword(s):  
Nervous System ◽  
Neuronal Activity ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Nervous System Development ◽  
Current Evidence ◽  
Mammalian Brain ◽  
Postnatal Neurogenesis ◽  
Proliferation And Differentiation ◽  
Activity Dependent

The addition of new neurons and oligodendroglia in the postnatal and adult mammalian brain presents distinct forms of gray and white matter plasticity. Substantial effort has been devoted to understanding the cellular and molecular mechanisms controlling postnatal neurogenesis and gliogenesis, revealing important parallels to principles governing the embryonic stages. While during central nervous system development, scripted temporal and spatial patterns of neural and glial progenitor proliferation and differentiation are necessary to create the nervous system architecture, it remains unclear what driving forces maintain and sustain postnatal neural stem cell (NSC) and oligodendrocyte progenitor cell (OPC) production of new neurons and glia. In recent years, neuronal activity has been identified as an important modulator of these processes. Using the distinct properties of neurotransmitter ionotropic and metabotropic channels to signal downstream cellular events, NSCs and OPCs share common features in their readout of neuronal activity patterns. Here we review the current evidence for neuronal activity-dependent control of NSC/OPC proliferation and differentiation in the postnatal brain, highlight some potential mechanisms used by the two progenitor populations, and discuss future studies that might advance these research areas further.

scholarly journals Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants

2020 ◽  
Vol 21 (6) ◽  
pp. 1944 ◽  
Author(s):  
Gilles Lalmanach ◽  
Ahlame Saidi ◽  
Paul Bigot ◽  
Thibault Chazeirat ◽  
Fabien Lecaille ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sulfhydryl Group ◽  
Redox Balance ◽  
Biological Functions ◽  
Cysteine Cathepsins ◽  
Michael Acceptors ◽  
Natural Inhibitors

Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments and also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation via their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with oxidative stress and their exposure resistance to oxidants. More specifically, there is only patchy information on the regulation of lung cysteine cathepsins, while the respiratory system is directly exposed to countless exogenous oxidants contained in dust, tobacco, combustion fumes, and industrial or domestic particles. Papain-like enzymes (clan CA, family C1, subfamily C1A) encompass a conserved catalytic thiolate-imidazolium pair (Cys25-His159) in their active site. Although the sulfhydryl group (with a low acidic pKa) is a potent nucleophile highly susceptible to chemical modifications, some cysteine cathepsins reveal an unanticipated resistance to oxidative stress. Besides an introductory chapter and peculiar attention to lung cysteine cathepsins, the purpose of this review is to afford a concise update of the current knowledge on molecular mechanisms associated with the regulation of cysteine cathepsins by redox balance and by oxidants (e.g., Michael acceptors, reactive oxygen, and nitrogen species).

scholarly journals Role of microRNA in muscle regeneration and diseases related to muscle dysfunction in atrophy, cachexia, osteoporosis, and osteoarthritis

2020 ◽  
Vol 9 (11) ◽  
pp. 798-807
Author(s):  
Joanna Brzeszczyńska ◽  
Filip Brzeszczyński ◽  
David F Hamilton ◽  
Robin McGregor ◽  
A. Hamish R. W. Simpson
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Current Knowledge ◽  
Published Data ◽  
Proliferation And Differentiation ◽  
Improve Patient Management ◽  
Limb Immobilization ◽  
Improve Patient

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data. Cite this article: Bone Joint Res 2020;9(11):798–807.

scholarly journals GILZ as a Regulator of Cell Fate and Inflammation

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Stefano Bruscoli ◽  
Carlo Riccardi ◽  
Simona Ronchetti
Keyword(s):  
Adverse Effects ◽  
Cell Fate ◽  
Immune Cells ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Outcomes ◽  
Proliferation And Differentiation ◽  
Adrenal Response ◽  
Anti Inflammatory

One of the human body’s initial responses to stress is the adrenal response, involving the release of mediators that include adrenaline and glucocorticoids (GC). GC are involved in controlling the inflammatory and immune response mechanisms. Of these, the molecular mechanisms that contribute to anti-inflammatory effects warrant more investigation. Previously, we found that GC induced GILZ (glucocorticoid-induced leucine zipper) quickly and widely in thymocytes, T lymphocytes, and other leukocytes. GILZ regulates the activation of cells and is an essential mediator of endogenous GC and the majority of GC anti-inflammatory effects. Further research in this regard could lead to the development of an anti-inflammatory treatment that yields the therapeutic outcomes of GC but without their characteristic adverse effects. Here, we examine the mechanisms of GILZ in the context of GC. Specifically, we review its role in the proliferation and differentiation of cells and in apoptosis. We also examine its involvement in immune cells (macrophages, neutrophils, dendritic cells, T and B lymphocytes), and in non-immune cells, including cancer cells. In conclusion, GILZ is an anti-inflammatory molecule that could mediate the immunomodulatory activities of GC, with less adverse effects, and could be a target molecule for designing new therapies to treat inflammatory diseases.

H2S signaling in redox regulation of cellular functions

2013 ◽  
Vol 91 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Youngjun Ju ◽  
Weihua Zhang ◽  
Yanxi Pei ◽  
Guangdong Yang
Keyword(s):  
Mammalian Cells ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Redox Homeostasis ◽  
Therapeutic Interventions ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Future Design ◽  
Cellular Effects

Hydrogen sulfide (H2S) is traditionally recognized as a toxic gas with a rotten-egg smell. In just the last few decades, H2S has been found to be one of a family of gasotransmitters, together with nitric oxide and carbon monoxide, and various physiologic effects of H2S have been reported. Among the most acknowledged molecular mechanisms for the cellular effects of H2S is the regulation of intracellular redox homeostasis and post-translational modification of proteins through S-sulfhydration. On the one side, H2S can promote an antioxidant effect and is cytoprotective; on the other side, H2S stimulates oxidative stress and is cytotoxic. This review summarizes our current knowledge of the antioxidant versus pro-oxidant effects of H2S in mammalian cells and describes the Janus-faced properties of this novel gasotransmitter. The redox regulation for the cellular effects of H2S through S-sulfhydration and the role of H2S in glutathione generation is also recapitulated. A better understanding of H2S-regualted redox homeostasis will pave the way for future design of novel pharmacological and therapeutic interventions for various diseases.

scholarly journals Oct4-mediated reprogramming induces embryonic-like microRNA expression signatures in human fibroblasts

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucie Peskova ◽  
Katerina Cerna ◽  
Jan Oppelt ◽  
Marek Mraz ◽  
Tomas Barta
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Microrna Expression ◽  
Plastic State ◽  
External Stimuli ◽  
Small Rnaseq

Abstract Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically “open” state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

scholarly journals Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants

2020 ◽  
Author(s):  
Gilles Lalmanach ◽  
Ahlame Saidi ◽  
Paul Bigot ◽  
Thibault Chazeirat ◽  
Fabien Lecaille ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sulfhydryl Group ◽  
Redox Balance ◽  
Biological Functions ◽  
Cysteine Cathepsins ◽  
Michael Acceptors ◽  
Natural Inhibitors

Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments but also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation by their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with an oxidative stress and their exposure resistance to oxidants. More specifically, there is only patchy information on the regulation of lung cysteine cathepsins, while the respiratory system is directly exposed to countless exogenous oxidants contained in dust, tobacco, combustion fumes, and industrial or domestic particles. Papain-like enzymes (clan CA, family C1, subfamily C1A) encompass a conserved catalytic thiolate-imidazolium pair (Cys25-His159) in their active site. Despite the sulfhydryl group (with a low acidic pKa) is a potent nucleophile highly susceptible to chemical modifications, some cysteine cathepsins reveal an unanticipated resistance to oxidative stress. Beside an introductory chapter and a peculiar attention to lung cysteine cathepsins, the purpose of this review is to afford a concise update of the current knowledge on molecular mechanisms associated to the regulation of cysteine cathepsins by redox balance and by oxidants (e.g. Michael acceptors, reactive oxygen and nitrogen species).

scholarly journals The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation of Rag Gene Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Kazuko Miyazaki ◽  
Masaki Miyazaki
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Chromatin Architecture ◽  
Cell Type Specific

Cell type-specific gene expression is driven through the interplay between lineage-specific transcription factors (TFs) and the chromatin architecture, such as topologically associating domains (TADs), and enhancer-promoter interactions. To elucidate the molecular mechanisms of the cell fate decisions and cell type-specific functions, it is important to understand the interplay between chromatin architectures and TFs. Among enhancers, super-enhancers (SEs) play key roles in establishing cell identity. Adaptive immunity depends on the RAG-mediated assembly of antigen recognition receptors. Hence, regulation of the Rag1 and Rag2 (Rag1/2) genes is a hallmark of adaptive lymphoid lineage commitment. Here, we review the current knowledge of 3D genome organization, SE formation, and Rag1/2 gene regulation during B cell and T cell differentiation.

scholarly journals Induced Neurons From Germ Cells in Caenorhabditis elegans

2021 ◽  
Vol 15 ◽  
Author(s):  
Iris Marchal ◽  
Baris Tursun
Keyword(s):  
Caenorhabditis Elegans ◽  
Regenerative Medicine ◽  
Cell Fate ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
C Elegans ◽  
Cell Fate Conversion ◽  
Induced Neurons

Cell fate conversion by the forced overexpression of transcription factors (TFs) is a process known as reprogramming. It leads to de-differentiation or trans-differentiation of mature cells, which could then be used for regenerative medicine applications to replenish patients suffering from, e.g., neurodegenerative diseases, with healthy neurons. However, TF-induced reprogramming is often restricted due to cell fate safeguarding mechanisms, which require a better understanding to increase reprogramming efficiency and achieve higher fidelity. The germline of the nematode Caenorhabditis elegans has been a powerful model to investigate the impediments of generating neurons from germ cells by reprogramming. A number of conserved factors have been identified that act as a barrier for TF-induced direct reprogramming of germ cells to neurons. In this review, we will first summarize our current knowledge regarding cell fate safeguarding mechanisms in the germline. Then, we will focus on the molecular mechanisms underlying neuronal induction from germ cells upon TF-mediated reprogramming. We will shortly discuss the specific characteristics that might make germ cells especially fit to change cellular fate and become neurons. For future perspectives, we will look at the potential of C. elegans research in advancing our knowledge of the mechanisms that regulate cellular identity, and what implications this has for therapeutic approaches such as regenerative medicine.

scholarly journals Mitochondrial Dynamics: impact on adult neural stem cell fate

2020 ◽  
Author(s):  
Rita Soares ◽  
Diogo M. Lourenço ◽  
Jonathan Verduyckt ◽  
Ana M. Sebastião ◽  
Sara Xapelli ◽  
...  
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Culture Conditions ◽  
Neurological Deficits ◽  
Mammalian Brain ◽  
Seeding Density ◽  
Brain Repair ◽  
Adult Neural Stem Cell

Neural stem cells (NSCs) are found in discrete regions of the mammalian brain. During adulthood, NSCs can be a source of new neurons and oligodendrocytes in neurological disorders. However, these newborn cells are not sufficient to overcome the neurological deficits involved by neural loss. Therefore, the identification of novel mechanisms responsible for modulating NSC fate represent a major key issue for future brain repair strategies. Several studies suggest that mitochondria have an important role in regulating NSC differentiation and lineage determination. However, the molecular mechanisms involved in this regulation remain unknown. Hence, our work aims to dissect how mitochondria biogenesis and dynamics can modulate the NSC differentiation into neurons or oligodendrocytes. For this, NSCs were obtained by isolating subventricular zone (SVZ) and dentate gyrus (DG) cells from P1-3 mouse models. Seeding density, culture conditions and number of passages were determined. Moreover, the multipotency of SVZ/DG-derived NSPCs, obtained from different passages, was also accessed. Additionally, expression of proteins involved in mitochondrial biogenesis and fusion/fission appear altered during NSPC differentiation, while mitochondrial network revealed different morphologies in cells from different lineages. The results obtained will provide novel findings concerning the role of mitochondrial dynamics in NSC fate.

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