GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188890 - 188890

Published: March 29, 2023

Language: Английский

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Ferroptosis in liver disease: new insights into disease mechanisms

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: Oct. 5, 2021

Abstract Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which morphologically, genetically, biochemically distinct from other well-known death. In recent years, has been quickly gaining attention in the field liver diseases, as predisposed to oxidative injury generally, primary characteristic most major diseases. current review, we first delineate three cellular defense mechanisms against (GPx4 mitochondria cytosol, FSP1 on plasma membrane, DHODH mitochondria), along with four canonical modulators (system Xc − , nuclear factor erythroid 2-related 2, p53, GTP cyclohydrolase-1). Next, review progress studies delineating molecular underlying pathophysiology several common diseases including ischemia/reperfusion-related (IRI), nonalcoholic fatty disease (NAFLD), alcoholic (ALD), hemochromatosis (HH), drug-induced (DILI), hepatocellular carcinoma (HCC). Furthermore, also highlight both challenges promises that emerged should be addressed pursued future investigations before regulation could adopted an effective therapeutic target clinical practice.

Language: Английский

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The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 1, 2021

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes gut microbiota and metabolites in I/R role on ferroptosis-induced This study aimed establish mouse model ileum organoid hypoxia/reoxygenation (H/R) explore during protective ability capsiate (CAT) against ferroptosis-dependent Intestinal induced disturbance significant metabolites. We that CAT metabolite levels preoperative stool patients undergoing cardiopulmonary bypass were negatively correlated with Furthermore, reduced injury vivo vitro. effects abolished by RSL3, an inhibitor glutathione peroxidase 4 (Gpx4), which negative regulator ferroptosis. also promote Gpx4 expression inhibit was abrogated JNJ-17203212, antagonist transient receptor potential cation channel subfamily V member 1 (TRPV1). suggests enhances inhibits ferroptosis activating TRPV1 injury, providing avenue for management

Language: Английский

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Selenium and Selenoproteins in Health

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 799 - 799

Published: May 8, 2023

Selenium is a trace mineral that essential for health. After being obtained from food and taken up by the liver, selenium performs various physiological functions in body form of selenoproteins, which are best known their redox activity anti-inflammatory properties. stimulates activation immune cells important system. also maintenance brain function. supplements can regulate lipid metabolism, cell apoptosis, autophagy, have displayed significant alleviating effects most cardiovascular diseases. However, effect increased intake on risk cancer remains unclear. Elevated serum levels associated with an type 2 diabetes, this relationship complex nonlinear. supplementation seems beneficial to some extent; however, existing studies not fully explained influence Further, more intervention trials needed verify or harmful

Language: Английский

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Targeting Ferroptosis: Pathological Mechanism and Treatment of Ischemia‐Reperfusion Injury

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

Published: Jan. 1, 2021

Ischemia‐reperfusion (I/R) is a pathological process that occurs in many organs and diseases. Reperfusion, recovery of blood flow, reoxygenation often lead to reperfusion injury. Drug therapy early can reduce tissue injury cell necrosis caused by ischemia, leading irreversible I/R Ferroptosis was clearly defined 2012 as newly discovered iron‐dependent, peroxide‐driven, nonapoptotic form regulated death. considered the cause This discovery provides new avenues for recognition treatment key factor leads organ failure. Given important role ferroptosis injury, there considerable interest potential targeted wide range injury‐related Recently, substantial progress has been made applying various The development regulators expected provide opportunities Herein, we analytically review mechanism related diseases from perspectives myocardial cerebral ischemic renal

Language: Английский

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Molecular mechanisms of ferroptosis and relevance to inflammation

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(2), P. 281 - 299

Published: Dec. 19, 2022

Language: Английский

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Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(2)

Published: Feb. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Language: Английский

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Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 17, 2022

Kidney is one of the most vulnerable organs in sepsis, resulting sepsis-associated acute kidney injury (SA-AKI), which brings about not only morbidity but also mortality sepsis. Ferroptosis a new kind death type cells elicited by iron-dependent lipid peroxidation, participates pathogenesis The aim this study was to verify occurrence ferroptosis SA-AKI and demonstrate that post-treatment with irisin could restrain alleviate via activating SIRT1/Nrf2 signaling pathway. We established model cecal ligation puncture (CLP) operation an vitro LPS-induced HK2 cells, respectively. Our result exhibited inhibited level ameliorated CLP mice, as evidenced reducing ROS production, iron content, MDA increasing GSH level, well alteration ferroptosis-related protein (GPX4 ACSL4) expressions renal, consistent inhibitor ferrostatin-1 (Fer-1). Additionally, we consistently observed accumulation, mitochondrial dysfunction LPS-stimulated HK-2 cells. Furthermore, our revealed activate pathways both vivo vitro. However, beneficial effects were weakened EX527 (an SIRT1) SIRT1 siRNA In conclusion, protect against through ferroptotic resistance

Language: Английский

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Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 14, 2022

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney (AKI). Ferroptosis non-apoptotic cell death that known to contribute renal I/R injury. Dexmedetomidine (Dex) has been shown exert anti-inflammatory and organ protective effects. This study aimed investigate the detailed molecular mechanism of Dex protects kidneys against through inhibiting ferroptosis. We established I/R-induced model in mice, OGD/R induced HEK293T cells damage vitro. RNA-seq analysis was performed for identifying potential therapeutic targets. differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related ferroptosis inflammation mice renal, which validated rodent renal. Liproxstatin-1, specific small-molecule inhibitor ferroptosis, significantly attenuated ferroptosis-mediated decreased LPO, MDA, LDH levels, increased GSH level. Inhibiting activity ACSL4 by Rosiglitazone (ROSI) resulted inflammation, as well reduced tissue damage, decreasing MDA level, increasing reducing COX2 GPx4 protein expression, suppressing TNF-α mRNA IL-6 levels. α2-adrenergic receptor (α2-AR) agonist effects Our results also revealed administration mitigated inhibited downregulated response following injury, were suppression ACSL4. In addition, overexpression abolishes Dex-mediated on cells, promotion expression α2-AR reversed role Dex. present indicated attenuates via α2-AR.

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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