The effects of oxidative stress on the development of atherosclerosis

2019 ◽  
Vol 400 (6) ◽  
pp. 711-732 ◽  
Author(s):  
Mohsen Khosravi ◽  
Adeleh Poursaleh ◽  
Ghasem Ghasempour ◽  
Shaikhnia Farhad ◽  
Mohammad Najafi
Keyword(s):  
Oxidative Stress ◽  
Cellular Proliferation ◽  
Nadh Oxidase ◽  
Macrophage Polarization ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidative Modification ◽  
Oxidative Enzymes ◽  
Matrix Remodeling ◽  
And Migration

Abstract Atherosclerosis is a cardiovascular disease (CVD) known widely world wide. Several hypothesizes are suggested to be involved in the narrowing of arteries during process of atherogenesis. The oxidative modification hypothesis is related to oxidative and anti-oxidative imbalance and is the most investigated. The aim of this study was to review the role of oxidative stress in atherosclerosis. Furthermore, it describes the roles of oxidative/anti-oxidative enzymes and compounds in the macromolecular and lipoprotein modifications and in triggering inflammatory events. The reactive oxygen (ROS) and reactive nitrogen species (RNS) are the most important endogenous sources produced by non-enzymatic and enzymatic [myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADH) oxidase and lipoxygenase (LO)] reactions that may be balanced with anti-oxidative compounds [glutathione (GSH), polyphenols and vitamins] and enzymes [glutathione peroxidase (Gpx), peroxiredoxins (Prdx), superoxide dismutase (SOD) and paraoxonase (PON)]. However, the oxidative and anti-oxidative imbalance causes the involvement of cellular proliferation and migration signaling pathways and macrophage polarization leads to the formation of atherogenic plaques. On the other hand, the immune occurrences and the changes in extra cellular matrix remodeling can develop atherosclerosis process.

Oxidative Stress and Cancer: The Role of Nrf2

2018 ◽  
Vol 18 (6) ◽  
pp. 538-557 ◽  
Author(s):  
Soraya Sajadimajd ◽  
Mozafar Khazaei
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Nuclear Import ◽  
Tyrosine Kinases ◽  
Oxidative Enzymes ◽  
Nuclear Accumulation ◽  
Constitutive Activation ◽  
Number Of Genes ◽  
Electrophilic Stress

Oxidative stress due to imbalance between ROS production and detoxification plays a pivotal role in determining cell fate. In response to the excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxifying factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is commonly degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination factors. However, high amount of ROS activates tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear import of Nrf2 and coordinated activation of cytoprotective gene expression. Nevertheless, deregulation of Nrf2 and/or Keap1 due to mutation and activated upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and induce proliferation, metastasis and chemoresistance. Owning to the interplay of ROS and Nrf2 signaling pathways with carcinogenesis, Nrf2 modulation seems to be important in the personalization of cancer therapy.

Acute Stress Induced Behavioral Deficits In Rats: Relationship With Oxidative Stress, Leptin And HPA Axis

2019 ◽  
Vol 41 (5) ◽  
pp. 859-859
Author(s):  
Erum Shireen Erum Shireen ◽  
Wafa Binte Ali Wafa Binte Ali ◽  
Maria Masroor Maria Masroor ◽  
Saeeda Bano Saeeda Bano ◽  
Samina Iqbal Samina Iqbal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Hpa Axis ◽  
Acute Stress ◽  
Antioxidant Properties ◽  
Oxidative Enzymes ◽  
Behavioral Deficits ◽  
Glucose Estimation ◽  
Dark Transition

Acute exposure to stress is connected to many disorders that promote the toxicity of oxygen radical generators leading to increase in the levels of enzymes and also the activation of the HPA axis. The present study uses a preclinical approach to elucidate some prospective stress-induced behavioral and biochemical effects. The aim of current study was to investigate the relationship between stress and behavioral changes after exposing animals to 2h immobilization stress. We also evaluated the concentration of corticosterone, glucose and endogenous leptin levels in unstressed and stressed animals to explore the possible role of HPA axis in the modulation of stressed induced behavioral deficits. Rats were divided into stressed and unstressed groups. Behavioral activities were monitored in open field activity and light dark transition box after the termination of 2h immobilization period. Animals were then decapitated and plasma samples were collected for catalase, SOD, corticosterone, and glucose estimation. Results showed that exposure to acute stress produced a significant decrease in the activity of rats in the novel environment (open field) and light dark transition box. On the other hand, concomitant elevated level of peripheral markers of oxidative stress such as oxidative enzymes, corticosterone and endogenous leptin were also observed. Therefore, current study seems to suggest an important role of compounds having antioxidant properties for the treatment of stress and related disorders.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

scholarly journals Role of Oxidative Stress in Heart Failure: Insights from Gene Transfer Studies

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1645
Author(s):  
Bart De Geest ◽  
Mudit Mishra
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Gene Therapy ◽  
Steady State ◽  
Gene Transfer ◽  
Oxidative Modification ◽  
Heme Oxygenase 1 ◽  
Therapy Studies ◽  
Pathological Remodeling

Under physiological circumstances, there is an exquisite balance between reactive oxygen species (ROS) production and ROS degradation, resulting in low steady-state ROS levels. ROS participate in normal cellular function and in cellular homeostasis. Oxidative stress is the state of a transient or a persistent increase of steady-state ROS levels leading to disturbed signaling pathways and oxidative modification of cellular constituents. It is a key pathophysiological player in pathological hypertrophy, pathological remodeling, and the development and progression of heart failure. The heart is the metabolically most active organ and is characterized by the highest content of mitochondria of any tissue. Mitochondria are the main source of ROS in the myocardium. The causal role of oxidative stress in heart failure is highlighted by gene transfer studies of three primary antioxidant enzymes, thioredoxin, and heme oxygenase-1, and is further supported by gene therapy studies directed at correcting oxidative stress linked to metabolic risk factors. Moreover, gene transfer studies have demonstrated that redox-sensitive microRNAs constitute potential therapeutic targets for the treatment of heart failure. In conclusion, gene therapy studies have provided strong corroborative evidence for a key role of oxidative stress in pathological remodeling and in the development of heart failure.

scholarly journals miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Macrophage Polarization ◽  
Vital Role ◽  
Luciferase Reporter ◽  
M2 Macrophage ◽  
And Migration

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

scholarly journals Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

2018 ◽  
Vol 50 (1) ◽  
pp. 246-260 ◽  
Author(s):  
Xin Liu ◽  
Chang Liu ◽  
Kun Shan ◽  
Shujie Zhang ◽  
Yi Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Differentially Expressed ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Double Staining ◽  
Human Lens Epithelial Cells ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

scholarly journals Pathophysiology of Vascular Stenosis and Remodeling in Moyamoya Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Brandon M. Fox ◽  
Kirsten B. Dorschel ◽  
Michael T. Lawton ◽  
John E. Wanebo
Keyword(s):  
Moyamoya Disease ◽  
Cellular Proliferation ◽  
Vascular Inflammation ◽  
Neointimal Hyperplasia ◽  
Arterial Stenosis ◽  
Molecular Pathways ◽  
Matrix Remodeling ◽  
Vascular Networks ◽  
Internal Elastic Lamina ◽  
And Migration

Moyamoya disease (MMD) and moyamoya syndrome (MMS) are progressive vascular pathologies unique to the cerebrovasculature that are important causes of stroke in both children and adults. The natural history of MMD is characterized by primary progressive stenosis of the supraclinoid internal carotid artery, followed by the formation of fragile collateral vascular networks. In MMS, stenosis and collateralization occur in patients with an associated disease or condition. The pathological features of the stenosis associated with MMD include neointimal hyperplasia, disruption of the internal elastic lamina, and medial attenuation, which ultimately lead to progressive decreases in both luminal and external arterial diameter. Several molecular pathways have been implicated in the pathophysiology of stenosis in MMD with functions in cellular proliferation and migration, extracellular matrix remodeling, apoptosis, and vascular inflammation. Importantly, several of these molecular pathways overlap with those known to contribute to diseases of systemic arterial stenosis, such as atherosclerosis and fibromuscular dysplasia (FMD). Despite these possible shared mechanisms of stenosis, the contrast of MMD with other stenotic pathologies highlights the central questions underlying its pathogenesis. These questions include why the stenosis that is associated with MMD occurs in such a specific and limited anatomic location and what process initiates this stenosis. Further investigation of these questions is critical to developing an understanding of MMD that may lead to disease-modifying medical therapies. This review may be of interest to scientists, neurosurgeons, and neurologists involved in both moyamoya research and treatment and provides a review of pathophysiologic processes relevant to diseases of arterial stenosis on a broader scale.

The regulation of E3 ubiquitin ligases Cbl and its cross talking in bone homeostasis

2020 ◽  
Vol 15 ◽  
Author(s):  
Xiaobin Yang ◽  
Dingjun Hao ◽  
Baorong He
Keyword(s):  
Cellular Proliferation ◽  
Bone Matrix ◽  
Osteoclast Differentiation ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Bone Homeostasis ◽  
And Migration ◽  
First Time ◽  
Definite Role

: The E3 ubiquitin ligases Cbl has been found play an important role in regulating cellular proliferation and migration. Whereas the excessive differentiation of osteoclast and/or its over expressing of resorptive functions could lead the pathological bone homeostasis by overly bone matrix degradation. Since the first time of the important role of Cbl in the regulating osteoclast differentiation (also named osteoclastogenesis) has been reported in decades ago. The extensively studies have been conducted for in-depth exploring the Cbl’s definite role during osteoclastogenesis, as well as its cross talking with other signaling pathways (such as: Src and PI3K signaling) in bone homeostasis. Herein, our current study aim to briefly conclude the current studies of osteoclastogenesis and the regulatory role of Cbl, as well as its cross-talking in bone homeostasis.

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