Reactions of lipid hydroperoxides and how they may contribute to ferroptosis sensitivity

Current Opinion in Chemical Biology, Год журнала: 2024, Номер 81, С. 102478 - 102478

Опубликована: Июнь 21, 2024

The accumulation of lipid hydroperoxides (LOOHs) has long been associated with numerous pathologies and more recently shown to drive a specific type cell death known as ferroptosis. In competition their detoxification by glutathione peroxidases, LOOHs can react both one-electron reductants oxidants afford radicals that initiate peroxidation (LPO) chain reactions leading LOOH. These alternatively undergo variety (primarily unimolecular) electrophilic species destabilize the membrane and/or cellular nucleophiles. While some reaction mechanisms lipid-derived electrophiles have for time, others only elucidated. Since LOOH (and related peroxides, LOOL) these various at different rates distinct product distributions structures, not all LOOLs) should be equivalently problematic - it in propensity further LPO or fragment electrophiles, permeabilization eventual death. Herein we briefly review fates discuss how they may contribute modulation sensitivity ferroptosis lipids.

Язык: Английский

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Yeast-Inspired Orally-Administered Nanocomposite Scavenges Oxidative Stress and Restores Gut Immune Homeostasis for Inflammatory Bowel Disease Treatment

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Excessive oxidative stress, dysregulated immune homeostasis, and disruption of the intestinal epithelial barrier are crucial features inflammatory bowel disease (IBD). Traditional treatments focusing solely on inflammation resolution remain unsatisfactory. Herein, a yeast-inspired orally administered nanocomposite was developed. First, MD@MPDA core fabricated by integrating manganese dioxide (MnO2) nanozymes onto diallyl trisulfide (H2S prodrug)-loaded mesoporous polydopamine nanoparticles (MPDA). Then, yeast cell wall (YCW) chosen to encapsulate MD@MPDA, namely, YMD@MPDA. The β-glucan embedded in YCW shell not only protected from harsh gastrointestinal environment but also allowed targeting enrichment inflamed colon. Furthermore, M1 macrophages triggered intracellular GSH-responsive H2S release pathological microenvironment. effectively alleviated responses MnO2-mediated ROS-scavenging H2S-participated immunomodulation. synergistic action contributed macrophage mitochondrial function restoration M2 polarization suppressing NOX4 signaling p38 MAPK pro-inflammatory signaling. In mice model dextran sulfate sodium (DSS)-induced IBD, multipronged manner scavenging remodeling innate adaptive reshaping gut microbiota caused YMD@MPDA ameliorated restored functions. Overall, provides promising codelivery strategy antioxidative gas prodrugs for comprehensive management IBD.

Язык: Английский

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How Membrane Phospholipids Containing Long-Chain Polyunsaturated Fatty Acids and Their Oxidation Products Orchestrate Lipid Raft Dynamics to Control Inflammation

Journal of Nutrition, Год журнала: 2024, Номер 154(9), С. 2862 - 2870

Опубликована: Июль 25, 2024

Язык: Английский

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Ferroptosis at the nexus of metabolism and metabolic diseases

Theranostics, Год журнала: 2024, Номер 14(15), С. 5826 - 5852

Опубликована: Янв. 1, 2024

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a crucial regulator human physiology and pathology. Increasing evidence showcases reciprocal relationship between ferroptosis dysregulated metabolism, propagating pathogenic vicious cycle that exacerbates pathology diseases, particularly metabolic disorders. Consequently, there rapidly growing interest in developing ferroptosis-based therapeutics. Therefore, comprehensive understanding the intricate interplay metabolism could provide invaluable resource for mechanistic insight therapeutic development. In this review, we summarize important substances associated pathways initiation progression, outline cascade responses disease development, overview roles mechanisms introduce methods detection, discuss perspectives ferroptosis, which collectively aim to illustrate view basic, translational, clinical science.

Язык: Английский

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J-Aggregated indocyanine green-loaded exosomes enable photoactivatable cytoplasmic delivery of STING agonist for targeted pancreatic cancer immunotherapy

Nano Today, Год журнала: 2025, Номер 62, С. 102727 - 102727

Опубликована: Март 25, 2025

Язык: Английский

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GPCRs in the round: SMA-like copolymers and SMALPs as a platform for investigating GPCRs

Archives of Biochemistry and Biophysics, Год журнала: 2024, Номер 754, С. 109946 - 109946

Опубликована: Фев. 22, 2024

G-protein-coupled receptors (GPCRs) are the largest family of membrane proteins, regulate a plethora physiological responses and therapeutic target for 30-40% clinically-prescribed drugs. They integral proteins deeply embedded in plasma where they activate intracellular signalling via coupling to G-proteins β-arrestin. GPCRs intimate association with bilayer lipids that lipid environment regulates functions GPCRs. This complex 'landscape' is both heterogeneous dynamic. GPCR function modulated by bulk properties including fluidity, microdomains, curvature, thickness asymmetry but also regulated specific lipid:GPCR binding, cholesterol anionic lipids. Understanding molecular mechanisms whereby very active area research currently. A major advance protein recent years was application poly(styrene-co-maleic acid) (SMA) copolymers. These spontaneously generate SMA particles (SMALPs) encapsulating nano-scale disc cell membrane, thereby removing historical need detergent preserving interaction. The focus this review how GPCR-SMALPs increasing our understanding structure at level. Furthermore, an number 'second generation' SMA-like copolymers have been reported recently. reviewed from context mechanisms. Moreover, their potential as novel platform downstream biophysical structural analyses assessed looking ahead, translational drug discovery programmes future considered.

Язык: Английский

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Organ-selective lipid nanoparticles for precise cancer therapy: Beyond liposomes and polymeric micelles

Chemical Engineering Journal, Год журнала: 2024, Номер 494, С. 153171 - 153171

Опубликована: Июнь 15, 2024

Язык: Английский

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Iron-Induced Lipid Oxidation Alters Membrane Mechanics Favoring Permeabilization

Langmuir, Год журнала: 2024, Номер 40(47), С. 25061 - 25068

Опубликована: Ноя. 12, 2024

Ferroptosis is a form of regulated necrosis characterized by the iron-dependent accumulation lipid peroxides in cell membranes. However, how oxidation via iron-mediated Fenton reactions affects biophysical properties cellular membranes and these changes contribute to opening plasma membrane pores are major questions field. Here, we dynamics alterations during induced onsite chemically defined vitro model systems. We find that vesicle permeabilization kinetically correlates with appearance malondialdehyde (MDA), product oxidation. Iron-induced also alters lateral organization supported bilayers (SLBs) phase coexistence time-dependent manner, reducing mismatch circularity liquid ordered domains, which indicates decrease line tension at boundaries. Further analysis oxidized SLBs force spectroscopy reveals significant average breakthrough upon oxidation, resulting from bilayer make it more susceptible permeabilization. Our findings suggest Fenton-like induces strong interactions mechanical leading reduced permeabilized state bilayer, promotes pore formation.

Язык: Английский

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Broadening horizons: research on ferroptosis in lung cancer and its potential therapeutic targets

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 23, 2025

Ferroptosis is a novel form of cell death distinct from traditional mechanisms, characterized by the accumulation iron ions and production lipid peroxides. It not only affects survival tumor cells but also closely linked to changes in microenvironment. Lung cancer one leading malignancies worldwide terms incidence mortality, its complex biological mechanisms resistance make treatment challenging. Recent studies have shown that ferroptosis plays key role onset progression lung cancer, with intricate regulatory influencing development response therapy. As research into deepens, related molecular pathways, such as glutamate metabolism, antioxidant defense, been gradually revealed. However, clinical practice, ferroptosis-based therapeutic strategies for are still their early stages. Challenges remain, including incomplete understanding specific ferroptosis, insufficient on factors, limited insight interactions within Therefore, effective modulation enhance remains an urgent issue. This review summarizes analyzes factors interaction microenvironment, further explores potential targeting ferroptosis. By synthesizing latest research, this paper aims provide new perspectives directions treatment, goal advancing applications.

Язык: Английский

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Mapping the future: bibliometric insights into ferroptosis and diabetic nephropathy

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, exerts substantial burden on healthcare systems globally. Emerging evidence highlights ferroptosis - an iron-dependent form cell death driven by lipid peroxidation and glutathione depletion as critical contributor to DN progression via oxidative stress, tubular injury, glomerular dysfunction. Despite increasing research interest, comprehensive synthesis trends mechanistic insights is lacking. This study integrated bibliometric analysis with review map the evolving landscape in DN, identify hotspots, propose future directions for therapeutic development. In total, 86 publications (2018-2023) were retrieved from Web Science Core Collection analyzed using CiteSpace VOSviewer. Co-occurrence networks, citation trends, keyword bursts examined delineate global contributions, collaborative emerging themes. Annual publication numbers surged 12-fold after 2020, China contributing highest proportion (60.4%), led institutions such Zhengzhou University. The United States America Germany showed high centrality networks. Key themes included peroxidase 4 (GPX4)-mediated antioxidant defenses, acyl-CoA synthetase long-chain family member (ACSL4)-mediated remodeling, iron dysregulation. Frontiers Endocrinology (nine articles) Free Radical Biology Medicine (highest count: 171) emerged pivotal platforms. Mechanistic analyses identified three defense axes (GPX4, FSP1/CoQ10, GCH1/BH4) type-specific vulnerabilities tubular, podocyte, endothelial cells. Preclinical agents, including ginkgolide B (GB) dapagliflozin, effectively restored homeostasis attenuated damage. Ferroptosis promising target yet its clinical translation remains infancy. Future efforts should prioritize large-scale trials, single-cell profiling, interdisciplinary integration bridge molecular precision therapies. provides roadmap advancing ferroptosis-targeted interventions emphasizing collaborations biomarker-driven strategies.

Язык: Английский

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