Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 171, P. 55 - 68

Published: May 8, 2021

Language: Английский

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RONS and Oxidative Stress: An Overview of Basic Concepts

Oxygen, Journal Year: 2022, Volume and Issue: 2(4), P. 437 - 478

Published: Oct. 10, 2022

Oxidative stress (OS) has greatly interested the research community in understanding damaging processes occurring cells. OS is triggered by an imbalance between reactive oxygen species (ROS) production and their elimination antioxidant system; however, ROS function as second messengers under physiological conditions. are produced from endogenous exogenous sources. Endogenous sources involve mitochondria, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), oxidases (NOXs), endoplasmic reticulum (ER), xanthine (XO), endothelial nitric oxide synthase (eNOs), others. In contrast, might be generated through ultraviolet (UV) light, ionizing radiation (IR), contaminants, heavy metals, among It can damage DNA, lipids, proteins if not controlled. To avoid oxidative damage, systems activated. present review, we focus on basic concepts of OS, highlighting nitrogen (RONS) derived internal external last elimination. Moreover, include cellular system regulation ability to decrease OS. External antioxidants also proposed alternatives ameliorate Finally, review diseases involving mechanisms.

Language: Английский

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Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 667 - 667

Published: April 25, 2021

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage the cardiac tissue. Naturally, reoxygenation has been recognized as treatment choice to recover blood flow through primary percutaneous coronary intervention. This gold standard therapy restore flow, but paradoxically it can also induce tissue injury. A number different studies animal models acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up 50% final infarct size. Oxidative stress plays critical role pathological process. Iron an essential mineral required variety vital biological functions potentially toxic effects. detrimental process induced by free iron ferroptosis, non-apoptotic type programmed cell death. Accordingly, efforts prevent ferroptosis settings have focused on use radical trapping antioxidants (RTAs), such liproxstatin-1 (Lip-1). Hence, necessary develop novel strategies IRI, thus improving clinical outcome patients with ischemic disease. The present review analyses inhibition special reference Lip-1 promising drug this clinicopathological context.

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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Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Ferroptosis is a nonapoptotic form of cell death characterized by iron‐dependent accumulation lipid hydroperoxides to lethal levels. Necroptosis, an alternative programmed necrosis, regulated receptor‐interacting protein (RIP) 1 activation and RIP3 mixed‐lineage kinase domain‐like (MLKL) phosphorylation. necroptosis both play important roles in the pathological progress ischemic stroke, which complex brain disease several pathways. In past few years, increasing evidence has suggested that crosstalk occurs between ferroptosis stroke. However, potential links stroke have not been elucidated yet. Hence, this review, we overview analyze mechanism underlying And find iron overload, one ferroptosis, leads mitochondrial permeability transition pore (MPTP) opening, aggravates RIP1 phosphorylation contributes necroptosis. addition, heat shock 90 (HSP90) induces promoting suppressing glutathione peroxidase 4 (GPX4) activation. work, try deliver new perspective exploration novel therapeutic targets for treatment

Language: Английский

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FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis

Metabolism, Journal Year: 2021, Volume and Issue: 122, P. 154840 - 154840

Published: July 29, 2021

Language: Английский

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Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy

Redox Biology, Journal Year: 2021, Volume and Issue: 48, P. 102185 - 102185

Published: Nov. 11, 2021

Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, clinical intervention effect not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics ferroptosis, are potential therapeutic targets. Here, we confirmed in vitro vivo at least autophagy, apoptosis, ferroptosis involved Dox cardiotoxicity-induced damage. When neonatal rat cardiomyocytes H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress thereby alleviate protect myocardium according functional, enzymatic, morphological indices. The underlying was verified involve upregulation activation AMP-activated protein kinase α2, which promoted adaptive increased energy supply, maintained mitochondrial function. We believe a candidate phytochemical against cardiotoxicity.

Language: Английский

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Autophagy mediates an amplification loop during ferroptosis

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 25, 2023

Ferroptosis, a programmed cell death, has been identified and associated with cancer various other diseases. Ferroptosis is defined as reactive oxygen species (ROS)-dependent death related to iron accumulation lipid peroxidation, which different from apoptosis, necrosis, autophagy, forms of death. However, accumulating evidence revealed link between autophagy ferroptosis at the molecular level suggested that involved in regulating iron-dependent peroxidation ROS during ferroptosis. Understanding roles pathophysiological processes may provide effective strategies for treatment ferroptosis-related In this review, we summarize current knowledge regarding regulatory mechanisms underlying ferroptosis, including metabolism, its association pathway. addition, discuss contribution elucidate role enhancer ROS-dependent

Language: Английский

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Therapeutic Targets for DOX-Induced Cardiomyopathy: Role of Apoptosis vs. Ferroptosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1414 - 1414

Published: Jan. 26, 2022

Doxorubicin (DOX) is the most widely used anthracycline anticancer agent; however, its cardiotoxicity limits clinical efficacy. Numerous studies have elucidated mechanisms underlying DOX-induced cardiotoxicity, wherein apoptosis has been reported as common final step leading to cardiomyocyte death. However, in past two years, involvement of ferroptosis, a novel programmed cell death, proposed. The purpose this review summarize historical background that led each form focusing on and molecular trigger Furthermore, based understanding, possible therapeutic strategies prevent DOX are outlined. DNA damage, oxidative stress, intracellular signaling, transcription factors, epigenetic regulators, autophagy, metabolic inflammation important factors apoptosis. Conversely, accumulation lipid peroxides, iron ion accumulation, decreased expression glutathione peroxidase 4 ferroptosis. In both cascades, mitochondria an site cardiotoxicity. last part focuses significance disruption mitochondrial homeostasis

Language: Английский

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Molecular Mechanisms of Ferroptosis and Relevance to Cardiovascular Disease

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2726 - 2726

Published: Sept. 1, 2022

Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Excessive iron induces ferroptosis promoting generation both soluble ROS via an iron-dependent Fenton reaction lipoxygenase (LOX) enzyme activity. Cytosolic glutathione peroxidase 4 (cGPX4) pairing with suppressor protein 1 (FSP1) mitochondrial (mGPX4) dihydroorotate dehydrogenase (DHODH) serve as two separate defense systems detoxify cytoplasmic well membrane, thereby defending against cells under normal conditions. However, disruption these may cause ferroptosis. Emerging evidence revealed plays essential role development diverse cardiovascular diseases (CVDs), such hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, COVID-19–related arrhythmias. Iron chelators, antioxidants, inhibitors, genetic manipulations alleviate aforementioned CVDs blocking pathways. In conclusion, critical pathogenesis various suppression cardiac is expected become potential therapeutic option. Here, we provide comprehensive review on molecular mechanisms involved its implications disease.

Language: Английский

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