SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via induction of NAD+ depletion-dependent activation of ATF3

Redox Biology, Journal Year: 2024, Volume and Issue: 69, P. 103030 - 103030

Published: Jan. 3, 2024

Ferroptosis is a type of programmed cell death resulting from iron overload-dependent lipid peroxidation, and could be promoted by activating transcription factor 3 (ATF3). SIRT1 an enzyme accounting for removing acetylated lysine residues target proteins consuming NAD+, but its role remains elusive in ferroptosis ATF3. In this study, we found was activated during the process RSL3-induced glioma ferroptosis. Moreover, aggravated activator SRT2183, suppressed SIRT inhibitor EX527 or when silenced with siRNA. These indicated sensitized cells to Furthermore, expressional upregulation nuclear translocation Silence ATF3 siRNA attenuated increases ferrous downregulation SLC7A11 GPX4 depletion cysteine GSH. Thus, inducting activation. Mechanistically, activation reinforced decline NAD+ FK866 that inhibit NAD + synthesis via salvage pathway, intracellular maintained at higher level supplement exogenous NAD+. Notably, caused RSL3 enhanced further inhibited EX527. consumption Finally, inducing reactive oxygen species-dependent AROS. Together, our study revealed AROS sensitizes ATF3-dependent inhibition GPX4.

Language: Английский

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The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

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Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(20), P. 3075 - 3089

Published: July 24, 2023

Resveratrol is an organic compound widely studied for its therapeutic uses. We investigated whether resveratrol exerts cardioprotective effects by inhibiting ferroptosis via the Sirt1/p53 pathway. A heart failure model was established aortic coarctation in Sirt1 knockout mice. The superoxide dismutase (SOD), glutathione (GSH) levels and mitochondrial morphology murine tissues were assessed at different time points to determine role of progression. cardiac function mice with evaluated determining brain natriuretic peptide (BNP) sST2 concentration conducting echocardiography. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) transfected p53 K382R mutant interference lentiviral vectors. Immunoprecipitation (IP) experiments performed investigate influences K382 acetylation SLC7A11 expression modulation. improved decelerated fibrosis progression failure. However, ability prevent treat lost after silencing Sirt1. reduced diminishing acetylation, reducing degradation SLC7A11, increasing GSH peroxidase 4 (GPX4) cells. In conclusion, activating pathway failure, decreased depletion inhibited ferroptosis, function.

Language: Английский

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Resveratrol protects against doxorubicin-induced cardiotoxicity by attenuating ferroptosis through modulating the MAPK signaling pathway

Toxicology and Applied Pharmacology, Journal Year: 2023, Volume and Issue: 482, P. 116794 - 116794

Published: Dec. 22, 2023

Doxorubicin (Dox) is a widely used antitumor agent with dose-dependent and cumulative cardiotoxic effects. Resveratrol (Res) natural non-flavonoid polyphenol that can potentially provide cardiovascular benefits. We aimed to estimate the protective effect of Res on Dox-induced cardiotoxicity (DIC) explore whether it was related attenuating ferroptosis. established DIC models in C57BL/6 J mice, H9C2 cardiomyoblasts, neonatal rat cardiomyocytes (NRCMs). further treated cells RSL3, ferroptosis agonist, investigate exerted effects through inhibiting Ferrostatin-1 (Fer-1) applied suppress Dox treatment caused cardiac dysfunction resulted apparent ferroptotic damage tissue, involving increased iron accumulation, glutathione depletion, expression markers, decreased peroxidase 4, which were alleviated by Fer-1 administration. These findings also confirmed Dox-treated NRCMs, effectively cytotoxicity Furthermore, protected from RSL3-induced cell death, similar Fer-1. Both RSL3 phosphorylation levels mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, p38, c-Jun N-terminal kinases; however, these changes hindered Res. This study demonstrates alleviates suppressing possibly modulating MAPK signaling pathway. Our results highlight targeting be potential cardioprotective strategy for DIC.

Language: Английский

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A Systematic Review on Advances in Management of Oxidative Stress-Associated Cardiovascular Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(8), P. 923 - 923

Published: July 29, 2024

Oxidative stress plays a significant role in the pathogenesis of cardiovascular diseases, such as myocardial ischemia/reperfusion injury, atherosclerosis, heart failure, and hypertension. This systematic review aims to integrate most relevant studies on oxidative management diseases. We searched literatures PubMed database using specific keywords. put emphasis those manuscripts that were published more recently higher impact journals. reviewed total 200 articles. examined current managements including supplements like resveratrol, vitamins C E, omega-3 fatty acids, flavonoids, coenzyme-10, which have shown antioxidative properties potential benefits. In addition, we pharmacological treatments newly discovered antioxidants nanoparticles show effects targeting pathways. Lastly, biomarkers, soluble transferrin receptor, transthyretin, cystatin evaluating antioxidant status identifying risk. By addressing mechanisms, this paper emphasizes importance maintaining balance between oxidants progression is registered with International Platform Registered Systematic Review Meta-analysis Protocols (INPLASY), registration # INPLASY202470064.

Language: Английский

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The Role of Stem Cells in the Treatment of Cardiovascular Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3901 - 3901

Published: March 31, 2024

Cardiovascular diseases (CVDs) are the leading cause of death and include several vascular cardiac disorders, such as atherosclerosis, coronary artery disease, cardiomyopathies, heart failure. Multiple treatment strategies exist for CVDs, but there is a need regenerative damaged heart. Stem cells broad variety with great differentiation potential that have immunomodulatory properties. studies evaluated efficacy stem in mesenchymal induced pluripotent cell-derived cardiomyocytes. These demonstrated can improve left ventricle ejection fraction, reduce fibrosis, decrease infarct size. Other investigated methods to survival, engraftment, functionality CVDs. The aim present review summarize current evidence on role how their efficacy.

Language: Английский

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321

Published: Aug. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Language: Английский

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From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 17, 2025

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology PCOS multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, dysregulation. Iron, critical mineral, not only plays role regulating female physiological functions the progression but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, form nonapoptotic cell death characterized by accumulation lipid peroxides. While numerous studies have explored ferroptosis patients animal models, precise mechanisms therapeutic implications remain inadequately understood. This review seeks elucidate pathophysiology contributory factors ferroptosis. Additionally, we examine diverse manifestations evaluate its role. Furthermore, introduce ferroptosis-related traditional Chinese medicines that may enhance understanding pathogenesis aid development targeted therapies for PCOS.

Language: Английский

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Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113598 - 113598

Published: March 1, 2025

Language: Английский

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Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(4), P. 2041 - 2076

Published: Feb. 23, 2024

Abstract In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form regulated cell death characterized iron‐dependent lipid peroxidation. This review delves into roles key phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis their underlying mechanisms. Emphasizing significance amino acid, lipid, iron metabolism, study elucidates diverse pathways through which these regulate ferroptosis. Notably, well‐known polyphenol, exhibits multifaceted interactions with cellular components involved regulation, providing distinctive therapeutic avenue. Stilbenes, another class, demonstrate promising influencing metabolism processes, contributing to ferroptotic death. Understanding intricate interplay between not only illuminates complex regulatory networks but also unveils avenues novel therapies. Exploring compounds inducers presents strategy targeted treatment, capitalizing on delicate balance article synthesizes current knowledge, aiming stimulate further research context ferroptosis‐mediated therapy.

Language: Английский

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