Oxidative Stress in Cardiovascular Diseases

Antioxidants, Journal Year: 2020, Volume and Issue: 9(9), P. 864 - 864

Published: Sept. 14, 2020

Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS generated as a by-product of mitochondrial respiration or metabolism by specific enzymes such superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, myeloperoxidases. Under physiological conditions, the low levels production equivalent to their detoxification, playing major role cellular signaling function. In pathological situations, particularly atherosclerosis hypertension, release exceeds endogenous antioxidant capacity, leading cell death. At cardiovascular levels, oxidative stress is highly implicated myocardial infarction, ischemia/reperfusion, heart failure. Here, we will first detail vessels. Indeed, able regulate multiple functions, proliferation, migration, Second, investigate implication diseases. Then, focus on produced NAPDH oxidase during endothelial dysfunction. Given importance at level, therapies could be real benefit. last part this review, new therapeutic strategies potentially involved protection currently under study.

Language: Английский

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The Role of Oxidative Stress in Atherosclerosis

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3843 - 3843

Published: Nov. 30, 2022

Atherosclerosis is a chronic inflammatory disease of the vascular system and leading cause cardiovascular diseases worldwide. Excessive generation reactive oxygen species (ROS) leads to state oxidative stress which major risk factor for development progression atherosclerosis. ROS are important maintaining health through their potent signalling properties. However, also activate pro-atherogenic processes such as inflammation, endothelial dysfunction altered lipid metabolism. As such, considerable efforts have been made identify characterise sources in blood vessels. Major enzymatic include NADPH oxidases, xanthine oxidase, nitric oxide synthases mitochondrial electron transport chains. The production balanced by ROS-scavenging antioxidant systems may become dysfunctional disease, contributing stress. Changes expression function antioxidants observed human atherosclerosis while vitro vivo animal models provided mechanistic insight into functions. There interest utilising molecules balance stress, yet clinical trials demonstrate any atheroprotective effects these molecules. Here we will review contribution discuss potential strategies ameliorate aspects disease.

Language: Английский

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Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway

Redox Biology, Journal Year: 2022, Volume and Issue: 54, P. 102389 - 102389

Published: June 29, 2022

The KEAP1-NRF2-ARE signaling pathway plays a central role in mediating the adaptive cellular stress response to oxidative and electrophilic chemicals. This canonical has been extensively studied reviewed past two decades, but rarely was it looked at from quantitative perspective. Signal amplification, i.e., ultrasensitivity, is crucially important for robust induction of antioxidant genes appropriate levels that can adequately counteract stresses. In this review article, we examined number well-known molecular events perspective with focus on how signal amplification be achieved. We illustrated, by using series mathematical models, redox-regulated protein sequestration, stabilization, translation, nuclear trafficking, DNA promoter binding, transcriptional – which are embedded network comprising KEAP1, NRF2, sMaf, p62, BACH1 may generate highly ultrasensitive NRF2 activation gene induction. emergence degree ultrasensitivity depend strengths protein-protein protein-DNA interaction abundances. A unique, understanding will help identify sensitive targets prevention therapeutics stress-related diseases develop adverse outcome models facilitate health risk assessment

Language: Английский

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Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2

Kidney International Reports, Journal Year: 2021, Volume and Issue: 6(7), P. 1775 - 1787

Published: May 4, 2021

Language: Английский

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Senolytics and senomorphics: Natural and synthetic therapeutics in the treatment of aging and chronic diseases

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 171, P. 169 - 190

Published: May 12, 2021

Language: Английский

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Small molecules regulating reactive oxygen species homeostasis for cancer therapy

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(1), P. 342 - 394

Published: Sept. 27, 2020

Elevated intracellular reactive oxygen species (ROS) and antioxidant defense systems have been recognized as one of the hallmarks cancer cells. Compared with normal cells, cells exhibit increased ROS to maintain their malignant phenotypes are more dependent on "redox adaptation" mechanism. Thus, there two apparently contradictory but virtually complementary therapeutic strategies for regulation prevent or treat cancer. The first strategy, that is, chemoprevention, is reduce either by suppressing production pathways employing antioxidants enhance clearance, which protects from transformation inhibits early stage tumorigenesis. second strategy ROS-mediated anticancer therapy, stimulates a toxicity threshold activate ROS-induced cell death pathways. Therefore, targeting ROS-related small-molecule candidates considered be promising treatment tumors. We herein briefly introduce source ROS, then focus small molecules regulate show efficacy in therapy perspective pharmacophores. Finally, we discuss several challenges developing agents based propose direction future development.

Language: Английский

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Mitochondrial Management of Reactive Oxygen Species

Antioxidants, Journal Year: 2021, Volume and Issue: 10(11), P. 1824 - 1824

Published: Nov. 17, 2021

Mitochondria in aerobic eukaryotic cells are both the site of energy production and formation harmful species, such as radicals other reactive oxygen known ROS. They contain an efficient antioxidant system, including low-molecular-mass molecules enzymes that specialize removing various types ROS or repairing oxidative damage biological molecules. Under normal conditions, is low, mitochondria, which their primary target, slightly damaged a similar way to cellular compartments, since released by mitochondria into cytosol negligible. As mitochondrial generation increases, they can deactivate components respiratory chain Krebs cycle, release high amount structures. More recently, feature does not specifically deal with intramitochondrial ROS, was discovered. Indeed, system detoxifies exogenous species at expense reducing equivalents generated mitochondria. Thus, also sink These observations highlight importance should be considered our understanding ROS-regulated processes. processes include cell signaling progression metabolic neurodegenerative disease.

Language: Английский

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Nrf2 and oxidative stress in liver ischemia/reperfusion injury

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(18), P. 5463 - 5479

Published: Dec. 30, 2021

In response to stress signal, nuclear factor‐erythroid 2‐related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety mechanisms, including regulation Keap1‐Nrf2 stability, transcriptional (NF‐ĸB, ATF3, ATF4), post‐transcriptional (miRNA), evidencing that responses are critical for maintenance homeostasis. Ischemia‐reperfusion (IR) injury major cause graft loss dysfunction clinical transplantation organ resection. During IR process, generation reactive oxygen species (ROS) leads damage from oxidative stress, oxidation biomolecules, mitochondrial dysfunction. Oxidative can trigger apoptotic necrotic cell death. Stress factors also result assembly inflammasome protein complex subsequent activation secretion proinflammatory cytokines. After activation, downstream upregulation act as primary cellular against cytotoxic effects help promote hepatic recovery during IR. The crosstalk between pathways liver potential therapeutic inducers will be discussed present review.

Language: Английский

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OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1875 - 1891.e7

Published: Sept. 15, 2022

Cardiomyopathy and heart failure are common manifestations in mitochondrial disease caused by deficiencies the oxidative phosphorylation (OXPHOS) system of mitochondria. Here, we demonstrate that cardiac-specific loss assembly factor Cox10 cytochrome c oxidase causes cardiomyopathy mice, which is associated with OXPHOS deficiency, lysosomal defects, an aberrant morphology. Activation peptidase Oma1 Cox10−/− mice results fragmentation induction integrated stress response (ISR) along Oma1-Dele1-Atf4 signaling axis. Ablation or Dele1 aggravates cardiomyopathy. ISR inhibition impairs cardiac glutathione metabolism, limits selenium-dependent accumulation peroxidase Gpx4, increases lipid peroxidation heart, ultimately culminating ferroptosis. Our a protective role Oma1-Dele1-mediated link ferroptosis to deficiency disease.

Language: Английский

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From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 18, 2023

Increased production and buildup of reactive oxygen species (ROS) can lead to various health issues, including metabolic problems, cancers, neurological conditions. Our bodies counteract ROS with biological antioxidants such as SOD, CAT, GPx, which help prevent cellular damage. However, if there is an imbalance between these antioxidants, it result in oxidative stress. This cause genetic epigenetic changes at the molecular level. review delves into how plays a role disorders caused by We also look animal models used for researching pathways. study offers insights mechanism, pathology, changes, assist drug development disease understanding.

Language: Английский

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