Superoxide Radicals in the Execution of Cell Death

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 501 - 501

Published: March 4, 2022

Superoxide is a primary oxygen radical that produced when an molecule receives one electron. dismutase (SOD) plays role in the cellular defense against oxidative insult by ROS. However, resulting hydrogen peroxide still reactive and, presence of free ferrous iron, may produce hydroxyl radicals and exacerbate diseases. Polyunsaturated fatty acids are preferred target radicals. Ferroptosis, type necrotic cell death induced lipid peroxides has attracted considerable interest because its pathogenesis many Radical electrons, namely those released from mitochondrial electron transfer complexes, enzymatic reactions, such as lipoxygenases, appear to cause peroxidation. While GPX4 most potent anti-ferroptotic enzyme known reduce alcohols, other antioxidative enzymes also indirectly involved protection ferroptosis. Moreover, several low molecular weight compounds include α-tocopherol, ascorbate, nitric oxide efficiently neutralize thereby suppressing The removal electrons early stages importance protecting ferroptosis diseases related stress.

Language: Английский

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Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression

Life Sciences, Journal Year: 2021, Volume and Issue: 284, P. 119942 - 119942

Published: Sept. 8, 2021

Language: Английский

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Anti-Inflammatory Nutrients and Obesity-Associated Metabolic-Inflammation: State of the Art and Future Direction

Nutrients, Journal Year: 2022, Volume and Issue: 14(6), P. 1137 - 1137

Published: March 8, 2022

Growing evidence supports the hypothesis that dietary factors may play a role in systemic low-grade chronic inflammation. Summary from randomized controlled trials has shown substantial effects on biomarkers of inflammation following adoption plant-based diets (including, but not limited to, Mediterranean diet), while consistent findings have been reported for higher intakes whole grains, fruits, and vegetables positive trends observed consumption legumes, pulses, nuts, olive oil. Among animal food groups, dairy products to best benefits inflammation, red meat egg neutral effects. The present review provides an overview mechanisms underlying relation between immune system, with focus specific macronutrient non-nutrient phytochemicals (polyphenols) Substantial differences within each group explain conflicting results obtained regarding foods high saturated fats carbohydrates, subtypes molecules (i.e., short-chain fatty acids or fiber vs. long chain free added sugars) when exploring diet as well importance matrix commixture context patterns. Dietary polyphenols oligopeptides hypothesized exert several functions, including regulation inflammatory response system. Overall, suggests affect system regardless obesity-related

Language: Английский

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Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Bioactive Materials, Journal Year: 2022, Volume and Issue: 22, P. 141 - 167

Published: Sept. 29, 2022

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and mortality rate of AKI, development effectively AKI is a huge unmet medical need research hotspot. Although existing evidence fully demonstrates that reactive oxygen nitrogen species (RONS) burst at site major contributor progression, heterogeneity, complexity, unique physiological structure make most antioxidant anti-inflammatory small molecule ineffective because lack targeting side effects. Recently, nanodrugs with intrinsic through control size, shape, surface properties have opened exciting prospects for treatment AKI. Many emerged address limitations current treatments. In this review, we systematically summarized first time about emerging exploit pathological features overcome traditional small-molecule achieve efficacy. First, analyzed structural characteristics main mechanism AKI: hypoxia, harmful substance accumulation-induced RONS renal despite multifactorial initiation heterogeneity Subsequently, introduced strategies used improve reviewed advances nano-RONS-sacrificial agents, nanozymes, nanocarriers antioxidants drugs. These demonstrated excellent therapeutic effects, such as greatly reducing oxidative stress damage, restoring function, low Finally, discussed challenges future directions translating into treatment.

Language: Английский

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NOX Dependent ROS Generation and Cell Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2086 - 2086

Published: Jan. 20, 2023

Reactive oxygen species (ROS) represent a group of high reactive molecules with dualistic natures since they can induce cytotoxicity or regulate cellular physiology. Among the ROS, superoxide anion radical (O2·-) is key redox signaling molecule prominently generated by NADPH oxidase (NOX) enzyme family and mitochondrial electron transport chain. Notably, altered balance deregulated are recognized hallmarks cancer involved in malignant progression resistance to drugs treatment. Since oxidative stress metabolism cells strictly intertwined, this review, we focus on emerging roles NOX enzymes as important modulators metabolic reprogramming cancer. The includes seven isoforms different activation mechanisms, widely expressed several tissues. In particular, dissect contribute NOX1, NOX2, NOX4 modulation highlight their potential role new therapeutic target for tumor rewiring.

Language: Английский

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The Influence of Gut Microbiota on Oxidative Stress and the Immune System

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1388 - 1388

Published: May 8, 2023

The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of entire organism. gut microbiota generates variety metabolites and thereby regulates many biological processes, such as regulation immune system. In gut, bacteria are direct contact with host. major challenge here prevent unwanted inflammatory reactions on one hand other ensure system can be activated when pathogens invade. Here REDOX equilibrium utmost importance. This controlled by either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for stable balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced status affects disrupting intracellular signaling promoting responses. we (i) focus most common reactive oxygen species (ROS) (ii) define transition from state oxidative stress. Further, (iii) describe ROS regulating Thereafter, (iv) examine influence homeostasis how shifts pro- anti-oxidative cellular conditions suppress promote responses inflammation.

Language: Английский

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PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(11), P. 1887 - 1910

Published: Oct. 30, 2023

Abstract Senescent cells remain metabolically active, but their metabolic landscape and resulting implications underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. display a PDK4-dependent increase aerobic glycolysis enhanced lactate production maintain mitochondrial respiration redox activity, thus adopting special form reprogramming. Medium from PDK4 + promotes the malignancy recipient cancer vitro, whereas inhibition causes tumor regression vivo. We find that reactive oxygen species via NOX1 to drive senescence-associated secretory phenotype, suppression reduces DNA damage severity restrains phenotype. In preclinical trials, alleviates physical dysfunction prevents age-associated frailty. Together, our study confirms hypercatabolic nature senescent reveals link between cellular production, possibly, age-related pathologies, including not limited cancer.

Language: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(17), P. 11632 - 11655

Published: Aug. 31, 2023

NADPH oxidases (NOXs) form a family of electron-transporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions these therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification selective inhibitors quite challenging, precluding pharmacologic demonstration targets in vivo. The aim this Perspective furnish an updated outlook about small-molecule described over last two decades. Structures, activities, vitro/in vivo specificity discussed, well biological assays used.

Language: Английский

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Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 10, 2023

Abstract The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to redox can have negative consequences, including the potential for cancer development and progression, which are closely linked series of processes, such adjustment reactive oxygen species (ROS) levels species, changes in antioxidant capacity, differential effects ROS on downstream cell fate immune capacity. tumor microenvironment (TME) exhibits complex interplay between immunity regulatory death, especially autophagy apoptosis, is crucially regulated by ROS. present study aims investigate multi-source affects autophagy, anti-tumor response TME mutual crosstalk these three processes. Given intricate role controlling immunity, we will further examine relationship traditional therapy It worth noting that discuss some ROS-related treatment options future studies.

Language: Английский

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