The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease

Nature Reviews Cardiology, Год журнала: 2022, Номер 20(1), С. 7 - 23

Опубликована: Июль 4, 2022

Язык: Английский

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Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 22, 2022

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in treatment of aging-related diseases. Sirtuin 1 (SIRT1), member NAD+-dependent deacetylase enzyme family, is extensively explored as potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against diseases such Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) reperfusion (MI/R), Atherosclerosis (AS), Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, regulates cellular senescence multiple processes, including SIRT1/Keap1/Nrf2/HO-1 SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mitochondrial damage, SIRT1/FoxO autophagy, SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin neuroprotective effects. In this review, we summarized improvement attenuation effect quercetin on relationship between relevant signaling pathways by SIRT1. Moreover, functional regulation markers function, autophagy apoptosis through was discussed. Finally, prospects extracellular vesicles (EVs) loading delivery, SIRT1-mediated EVs signal carriers treating diseases, well discussed ferroptosis alleviation to protect via activating Generally, may serve promising inhibiting reducing responses, restoring dysfunction.

Язык: Английский

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Empagliflozin attenuates the renal tubular ferroptosis in diabetic kidney disease through AMPK/NRF2 pathway

Free Radical Biology and Medicine, Год журнала: 2022, Номер 195, С. 89 - 102

Опубликована: Дек. 27, 2022

Язык: Английский

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Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives

Biomolecules, Год журнала: 2022, Номер 12(9), С. 1227 - 1227

Опубликована: Сен. 2, 2022

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds quality life these patients. Considering DKD main cause end-stage renal disease (ESRD) in developed countries, extensive research currently investigating matrix pathophysiology. Hyperglycemia, inflammation oxidative stress (OS) are mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-β, NF-κB, MCP-1, VCAM-1, ICAM-1) activation diverse pathways PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state impairment antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations filtration unit. Hitherto, wide spectrum pre-clinical clinical studies shows beneficial use NRF2-inducing strategies, NRF2 activators Bardoxolone methyl, Curcumin, Sulforaphane their analogues), other natural properties treatment. However, limitations regarding lack larger trials, solubility or delivery hamper implementation for use. Therefore, review, we will discuss mechanisms, especially NRF2/KEAP1/ARE involvement, while highlighting potential therapeutic approaches that target via OS.

Язык: Английский

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Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

Cell Death and Disease, Год журнала: 2023, Номер 14(2)

Опубликована: Фев. 16, 2023

Abstract The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in cardiovascular due its key contribution detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption GSH a critical element pathogenesis myocardial injury. Meanwhile, newly proposed type cell death, ferroptosis, has been demonstrated closely related system, which affects process outcome Moreover, facing various pathological challenges, mammalian heart, possesses high levels mitochondria weak capacity, susceptible oxidant production oxidative damage. Therefore, targeted enhancement along with prevention ferroptosis myocardium promising therapeutic strategy. In this review, we first systematically describe physiological functions anabolism as well effects on cardiac Then, discuss relationship between comprehensive summary activation strategies presented, where mainly identify several herbal monomers, may provide valuable guidelines for exploration new approaches.

Язык: Английский

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6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 12

Опубликована: Дек. 31, 2022

Background. Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments consequently increase risk of mortality. Objective. To characterize the therapeutic effect 6-gingerol (6-G) on DCM identify its potential mechanism. Methods. In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet STZ, followed low-dose (25 mg/kg) high-dose (75 6-G intervention. For an in vitro model, H9c2 rat cardiomyoblast cells were stimulated with high glucose ( glucose = 33 mM) palmitic acid (100 μM) then treated μM). Histological echocardiographic analyses used assess cardiac structure function DCM. Western blotting, ELISA, real-time qPCR expression ferroptosis, inflammation, Nrf2/HO-1 pathway-related proteins RNAs. Protein collagen I III assessed immunohistochemistry, kits assay SOD, MDA, iron levels. Results. The results showed that decreased both mouse cell models hypertrophy interstitial fibrosis attenuated treatment resulted improved heart function. inhibited ferroptosis-related protein FACL4 content enhanced anti-ferroptosis-related GPX4. addition, also diminished secretion inflammatory cytokines, including IL-1β, IL-6, TNF-α. activated pathway, antioxidative stress capacity proved increased activity MDA production. Compared vivo, could produce similar effect. Conclusion. These findings suggest protect against mechanism ferroptosis inhibition inflammation reduction via enhancing pathway.

Язык: Английский

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Canagliflozin mitigates ferroptosis and improves myocardial oxidative stress in mice with diabetic cardiomyopathy

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Окт. 14, 2022

Canagliflozin (Cana), an anti-diabetes drug belongs to sodium-glucose cotransporter 2 inhibitor, is gaining interest because of its extra cardiovascular benefits. Ferroptosis a new mode cell death, which can promote the occurrence diabetic cardiomyopathy (DCM). Whether Cana alleviate DCM by inhibiting ferroptosis focus this study. Here, we induced models in C57BL6 mice and treated with Cana. Meanwhile, order exclude hypoglycemic effect, high glucose model H9C2 cells were established. In vivo study, observed that could effectively damage cardiac function mice, including increasing lactate dehydrogenase (LDH) troponin I (cTnI), alleviating myocardial fiber breakage, inflammation, collagen deposition mitochondrial structural disorder. We evaluated reactive oxygen species (ROS) levels DCFH-DA BODIPY 581/591 C11, vitro reduced ROS lipid glucose. JC-1 fluorochrome assay showed decreased membrane potential (MMP) was increased Furthermore, inhibitory effects on oxidative stress verified protein carbonyl (PCO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH). As key inducer ferroptosis, total iron Fe 2+ be inhibited both . addition, western blot results indicated expression ferritin heavy-chain (FTN-H) down-regulated, cystine-glutamate antiporter (xCT) up-regulated cells, suggesting inhibit balancing homeostasis promoting system Xc - /GSH/GPX4 axis DCM. These findings underscore fact plays important role development progression targeting may novel strategy for prevention treatment. conclusion, exert some benefits attenuating ferroptosis.

Язык: Английский

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AMPK and NRF2: Interactive players in the same team for cellular homeostasis?

Free Radical Biology and Medicine, Год журнала: 2022, Номер 190, С. 75 - 93

Опубликована: Июль 31, 2022

NRF2 (Nuclear factor E2 p45‐related 2) is a stress responsive transcription lending cells resilience against oxidative, xenobiotic, and also nutrient or proteotoxic insults. AMPK (AMP-activated kinase), considered as prime regulator of cellular energy homeostasis, not only tunes metabolism to provide the cell at any time with sufficient ATP building blocks, but controls redox balance inflammation. Due observed overlapping responses upon activation common stressors impinging on both signaling, it plausible assume that signaling may interdepend cooperate readjust homeostasis. After short introduction two players this narrative review paints current picture how might interact molecular level, highlights their possible crosstalk in selected examples pathophysiology bioactivity drugs phytochemicals.

Язык: Английский

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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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Regulated cell death pathways in cardiomyopathy

Acta Pharmacologica Sinica, Год журнала: 2023, Номер 44(8), С. 1521 - 1535

Опубликована: Март 13, 2023

Язык: Английский

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