Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107258 - 107258

Опубликована: Июнь 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Язык: Английский

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3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair

ACS Biomaterials Science & Engineering, Год журнала: 2024, Номер 10(4), С. 2451 - 2462

Опубликована: Март 1, 2024

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated three-dimensional (3D) printed conductive patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property electrical conductivity. The MSC@GO can be attached to the epicardium via adhesion provide strong integration infarcted hearts, well regeneration support area, thereby up-regulating expression connexin 43 (Cx43) resulting effective MI vivo. addition, also triggers apoptosis damage cardiomyocytes (CMs), hindering normal heart. GO exhibit protective effect against implanted MSCs. mouse model MI, implantation supported by reducing cell apoptosis, promoting gap protein Cx43 expression, then boosting Together, this study demonstrated that versatile conductivity function could therefore candidate repair.

Язык: Английский

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Pyroptosis in myocardial ischemia/reperfusion and its therapeutic implications

European Journal of Pharmacology, Год журнала: 2024, Номер 971, С. 176464 - 176464

Опубликована: Март 9, 2024

Язык: Английский

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Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 4, 2025

The study aimed to elucidate the underlying pharmacological mechanism of traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and vitro anoxia/reoxygenation (A/R) models were constructed. results demonstrated that pretreatment effectively alleviated MIRI, as manifested diminishing levels serum CK-MB LDH, mitigating extent infarction enhancing cardiac functionality. Additionally, significantly histopathological damage MIRI-treated myocardium, evidenced HE staining TUNEL assay. vitro, A/R-induced decreasing LDH levels, increasing cellular activity, inhibiting autophagic lysosomal overactivation, oxidative stress (ROS, LIP ROS, MDA), antioxidant defense (SOD, GSH-Px), P62 protein expression while LC3II/I ratio. Furthermore, inhibited apoptosis maintained mitochondrial homeostasis up-regulating Hairy Enhancer Split-1 (HES1) protein, which was crucial for its cardioprotective effects. Nevertheless, efficacy negated via knockdown HES1 pAD/HES1-shRNA transfection. conclusion, ameliorated HES1-mediated MIRI-induced autophagy, apoptosis, dysfunction.

Язык: Английский

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UPF1 Alleviates Myocardial Ischemia-Reperfusion Injury by Regulating SMURF2-Mediated Ubiquitination Degradation of FOXA2

Korean Circulation Journal, Год журнала: 2025, Номер 55

Опубликована: Янв. 1, 2025

Myocardial ischemia/reperfusion injury (MIRI) is an important factor affecting therapeutic effect and prognosis of acute myocardial infarction. Here, the effects up-frameshift 1 (UPF1) on cardiomyocyte apoptosis in MIRI were evaluated. H9C2 cells cultured under hypoxia/reoxygenation (H/R) condition. The expression UPF1, SMAD-specific E3 ubiquitin ligase 2 (SMURF2), forkhead box A2 (FOXA2), protease-activated receptor 4 (PAR4), Bax, Cleaved caspase-3 was assessed utilizing reverse transcription quantitative polymerase chain reaction western blot. Cell viability measured by Counting Kit-8 flow cytometry. Infarct area examined tetrazolium chloride staining (I/R) rat model. HE immunohistochemistry evaluated UPF1 expression, respectively. Terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling tested apoptosis. RNA immunoprecipitation, chromatin immunoprecipitation dual luciferase assay verified molecular interactions. FOXA2 ubiquitination detected assay. SMURF2 mRNA stability actinomycin D treatment. effectively suppressed induced H/R inhibiting PAR4 at transcriptional level. Degradation facilitated through SMURF2-mediated ubiquitination. Increased resulted a reduction H/R-induced apoptosis, improved dysfunction caused I/R vivo. influenced decay mRNA, leading to decrease its expression. Through SMURF2/FOXA2/PAR4 axis, triggered H/R. By suppressing stability, upregulated inhibit PAR4, inhibition during MIRI, which provides new targets for

Язык: Английский

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MGST1 overexpression ameliorates mitochondrial dysfunction and ferroptosis during myocardial ischemia/reperfusion injury after heart transplantation

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 299, С. 140135 - 140135

Опубликована: Янв. 21, 2025

Язык: Английский

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SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 183, С. 117832 - 117832

Опубликована: Янв. 22, 2025

Язык: Английский

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Ferroptosis induced by environmental pollutants and its health implications

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 24, 2025

Abstract Environmental pollution represents a significant public health concern, with the potential risks associated environmental pollutants receiving considerable attention over an extended period. In recent years, substantial body of research has been dedicated to this topic. Since discovery ferroptosis, iron-dependent programmed cell death typically characterized by lipid peroxidation, in 2012, there have advances study its role and mechanism various diseases. A growing number studies also demonstrated involvement ferroptosis damage caused organism pollutants, molecular mechanisms involved partially elucidated. The targeting be effective means ameliorating PM2.5, organic inorganic ionizing radiation. This review begins providing summary most important ferroptosis. It then proceeds offer critical analysis effects induced pollutants. Furthermore, as is case all rapidly evolving areas, are numerous unanswered questions challenges pertaining pollutant-induced which we discuss attempt provide some directions clues for future field.

Язык: Английский

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Preconditioning with acteoside ameliorates myocardial ischemia‑reperfusion injury by targeting HSP90AA1 and the PI3K/Akt signaling pathway

Molecular Medicine Reports, Год журнала: 2025, Номер 31(3)

Опубликована: Янв. 24, 2025

The present study aimed to investigate the cardioprotective effects of acteoside (AC) on myocardial ischemia‑reperfusion injury (MIRI). To meet this aim, a network pharmacological analysis was conducted search for key genes and signaling pathways associated with AC MIRI. infarct size rat heart evaluated using 2,3,5‑triphenyltetrazolium chloride staining, serum levels creatine kinase MB isoenzyme, cardiac troponin I, malondialdehyde superoxide dismutase were subsequently detected in an vivo experiment. inhibitory effect oxidative stress further confirmed by assessing intracellular accumulation reactive oxygen species (ROS). Hematoxylin eosin staining carried out observe histopathological damage. anti‑apoptotic determined terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay Hoechst 33342 expression apoptosis‑associated proteins tissue assessed immunohistochemical analysis. In addition, cell viability Cell Counting Kit‑8 assay, target MIRI western blot results suggested that pretreatment could mitigate MIRI‑induced damage, apoptosis. elevated Bcl‑2 levels, reduced caspase‑3 Bax tissue. vitro, both led increased rate survival alleviated stress, as demonstrated decreased level ROS accumulation. Moreover, guided analysis, heat‑shock protein 90AA1 (HSP90AA1) phosphoinositide 3‑kinase (PI3K)/serine‑threonine (Akt) pathway emerged targets action against Furthermore, showed significant increase activity PI3K/Akt pathway, addition glycogen synthase kinase‑3β HSP90AA1. Taken together, findings revealed may exert through suppressing apoptosis regulating proteins.

Язык: Английский

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