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 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 Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals The Impact of Medium Chain and Polyunsaturated ω-3-Fatty Acids on Amyloid-β Deposition, Oxidative Stress and Metabolic Dysfunction Associated with Alzheimer´s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1991
Author(s):  
Janine Mett
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Energy Metabolism ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Membrane Integrity ◽  
Amyloid Β ◽  
The Elderly ◽  
Medium Chain ◽  
The Impact

Alzheimer’s disease (AD), the most common cause of dementia in the elderly population, is closely linked to a dysregulated cerebral lipid homeostasis and particular changes in brain fatty acid (FA) composition. The abnormal extracellular accumulation and deposition of the peptide amyloid-β (Aβ) is considered as an early toxic event in AD pathogenesis, which initiates a series of events leading to neuronal dysfunction and death. These include the induction of neuroinflammation and oxidative stress, the disruption of calcium homeostasis and membrane integrity, an impairment of cerebral energy metabolism, as well as synaptic and mitochondrial dysfunction. Dietary medium chain fatty acids (MCFAs) and polyunsaturated ω-3-fatty acids (ω-3-PUFAs) seem to be valuable for disease modification. Both classes of FAs have neuronal health-promoting and cognition-enhancing properties and might be of benefit for patients suffering from mild cognitive impairment (MCI) and AD. This review summarizes the current knowledge about the molecular mechanisms by which MCFAs and ω-3-PUFAs reduce the cerebral Aβ deposition, improve brain energy metabolism, and lessen oxidative stress levels.

scholarly journals In Sickness and in Health: The Oxygen Reactive Species and the Bone

2021 ◽  
Vol 9 ◽  
Author(s):  
Joana Reis ◽  
António Ramos
Keyword(s):  
Oxidative Stress ◽  
Cell Population ◽  
Population Differentiation ◽  
Current Knowledge ◽  
Redox Balance ◽  
Bone Cell ◽  
Reactive Species ◽  
Mechanical Stimuli ◽  
Therapeutic Goals ◽  
And Control

Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.

scholarly journals Nitric Oxide and Oxidative Stress-Mediated Cardiovascular Functionality: From Molecular Mechanism to Cardiovascular Disease

2020 ◽  
Author(s):  
Weilue He ◽  
Maria Paula Kwesiga ◽  
Eyerusalem Gebreyesus ◽  
Sijia Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular System ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Muscle Relaxation ◽  
Redox Balance ◽  
Heart Infarction ◽  
Artery Disease

The underlying pathology of most cardiovascular diseases (CVDs) such as coronary artery disease, high blood pressure, and stroke involves decreased cardiovascular contractility and anatomic alterations in cardiovascular structures. Nitric oxide (NO) regulates vascular tone and contractile function of myocardium and maintains blood vessel homeostasis. Interestingly, the effect of NO is like a double-edged sword in the body. Insufficient NO causes hypertension and atherosclerosis, while an overproduction of NO may foster inflammation and cause heart infarction and shock. In addition, growing evidences have shown that oxidative stress plays pivotal roles in the initiation and progression of CVDs. This chapter will discuss in detail the roles NO plays in the cardiovascular system under both physiological and pathological conditions. We will focus on: (1) the molecular mechanism of cardiovascular contraction, (2) NO/Ca2+-induced muscle relaxation, (3) NO-related structural change in blood vessels, and (4) redox balance in the cardiovascular system. The relationships between these molecular mechanisms and the characteristics of CVDs will be highlighted.

scholarly journals MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4370
Author(s):  
Montserrat Climent ◽  
Giacomo Viggiani ◽  
Ya-Wen Chen ◽  
Gerald Coulis ◽  
Alessandra Castaldi
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Redox Balance ◽  
Chronic Obstructive ◽  
Transcriptional Level ◽  
Control Mechanisms ◽  
Redox Equilibrium ◽  
Obstructive Pulmonary Disease

Reactive oxygen species (ROS) affect many cellular functions and the proper redox balance between ROS and antioxidants contributes substantially to the physiological welfare of the cell. During pathological conditions, an altered redox equilibrium leads to increased production of ROS that in turn may cause oxidative damage. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level contributing to all major cellular processes, including oxidative stress and cell death. Several miRNAs are expressed in response to ROS to mediate oxidative stress. Conversely, oxidative stress may lead to the upregulation of miRNAs that control mechanisms to buffer the damage induced by ROS. This review focuses on the complex crosstalk between miRNAs and ROS in diseases of the cardiac (i.e., cardiac hypertrophy, heart failure, myocardial infarction, ischemia/reperfusion injury, diabetic cardiomyopathy) and pulmonary (i.e., idiopathic pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, lung cancer) compartments. Of note, miR-34a, miR-144, miR-421, miR-129, miR-181c, miR-16, miR-31, miR-155, miR-21, and miR-1/206 were found to play a role during oxidative stress in both heart and lung pathologies. This review comprehensively summarizes current knowledge in the field.

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 Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

2014 ◽  
Vol 2014 ◽  
pp. 1-26 ◽  
Author(s):  
Bechan Sharma ◽  
Shweta Singh ◽  
Nikhat J. Siddiqi
Keyword(s):  
Oxidative Stress ◽  
Heavy Metals ◽  
Associated Factors ◽  
Current Knowledge ◽  
Toxic Metal ◽  
The Body ◽  
Biological Functions ◽  
Synthetic Antioxidants ◽  
Redox Systems ◽  
Carcinogenic Effects

Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis. The present review illustrates an account of the current knowledge about the effects of heavy metals (mainly arsenic, lead, mercury, and cadmium) induced oxidative stress as well as the possible remedies of metal(s) toxicity through natural/synthetic antioxidants, which may render their effects by reducing the concentration of toxic metal(s). This paper primarily concerns the clinicopathological and biomedical implications of heavy metals induced oxidative stress and their toxicity management in mammals.

Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

2017 ◽  
Vol 8 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Myriam Lazard ◽  
Marc Dauplais ◽  
Sylvain Blanquet ◽  
Pierre Plateau
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Model Organism ◽  
Protein Homeostasis ◽  
Recent Advances ◽  
Inorganic Selenium ◽  
Protein Thiols ◽  
Selenoamino Acids ◽  
High Doses

AbstractSelenium is an essential trace element due to its incorporation into selenoproteins with important biological functions. However, at high doses it is toxic. Selenium toxicity is generally attributed to the induction of oxidative stress. However, it has become apparent that the mode of action of seleno-compounds varies, depending on its chemical form and speciation. Recent studies in various eukaryotic systems, in particular the model organism Saccharomyces cerevisiae, provide new insights on the cytotoxic mechanisms of selenomethionine and selenocysteine. This review first summarizes current knowledge on reactive oxygen species (ROS)-induced genotoxicity of inorganic selenium species. Then, we discuss recent advances on our understanding of the molecular mechanisms of selenocysteine and selenomethionine cytotoxicity. We present evidences indicating that both oxidative stress and ROS-independent mechanisms contribute to selenoamino acids cytotoxicity. These latter mechanisms include disruption of protein homeostasis by selenocysteine misincorporation in proteins and/or reaction of selenols with protein thiols.

scholarly journals The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 632
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cancer Development ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
The Past ◽  
Cancer Phenotypes ◽  
Coding Potential

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

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