Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis DOI Creative Commons
Jianmei Chen, Shuo Qiu, Yang Liu

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 2, 2024

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), thus limits use doxorubicin (DOX) clinic. Here, we further showed that cardiac ferroptosis induced DOX mice was attributed to up-regulation Hmox1, as knockdown Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed ultrasound microbubble destruction (UTMD) heart region. UTMD greatly facilitated exosome heart. Consistently, assisted exosomal siHomox1 nearly blocked subsequent cardiotoxicity doxorubicin. In summary, our findings reveal upregulation HMOX1 induces cardiomyocytes UTMD-assisted siHmox1 can be used potential therapeutic strategy for DIC.

Language: Английский

Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future DOI Creative Commons

Wenxi Fang,

Saiyang Xie, Wei Deng

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: March 21, 2024

Abstract Cardiovascular diseases (CVDs) are the main that endanger human health, and their risk factors contribute to high morbidity a rate of hospitalization. Cell death is most important pathophysiology in CVDs. As one cell mechanisms, ferroptosis new form regulated (RCD) broadly participates CVDs (such as myocardial infarction, heart transplantation, atherosclerosis, failure, ischaemia/reperfusion (I/R) injury, atrial fibrillation, cardiomyopathy (radiation-induced cardiomyopathy, diabetes sepsis-induced cardiac doxorubicin-induced iron overload hypertrophic cardiomyopathy), pulmonary arterial hypertension), involving regulation, metabolic mechanism lipid peroxidation. This article reviews recent research on regulation its relationship with occurrence treatment CVDs, aiming provide ideas targets for clinical diagnosis by clarifying latest progress research. Graphical • The identification, development history characterization ferroptosis. role different subcellular organelles organelle-specific regulators includes metabolism, amino acid metabolism. cardiovascular cells diseases. efficacy pathological involved

Language: Английский

Citations

22
Inhibition of METTL3 ameliorates doxorubicin-induced cardiotoxicity through suppression of TFRC-mediated ferroptosis DOI Creative Commons
Lin Wu, Yuxin Du, Litao Wang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103157 - 103157

Published: April 12, 2024

Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use greatly limited by the life-threatening cardiotoxicity. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. Nonetheless, it remains elusive whether m6A and methyltransferase METTL3 are involved progression DOX-induced cardiotoxicity (DIC). Mice were administrated with DOX (accumulative dosage 20 mg/kg) repeatedly to establish chronic DIC model. Cardiomyocyte-specific conditional knockout mice employed evaluate effects altered on DIC. The cardiomyocyte ferroptosis also examined response stimulation. led increased levels expression cardiomyocytes c-Jun-dependent manner. METTL3-knockout exhibited improved cardiac function, remodeling injury following insult. Besides, inhibition alleviated iron accumulation cardiomyocytes, whereas overexpression exerted opposite effects. Mechanistically, promoted TFRC mRNA, critical gene governing uptake, enhanced stability through recognition reader protein, IGF2BP2. Moreover, pharmacological administration highly selective inhibitor STM2457 effectively ameliorated mice. plays cardinal role etiology regulating metabolism modification. Inhibition might be potential therapeutic avenue for

Language: Английский

Citations

21
PM2.5-induced iron homeostasis imbalance triggers cardiac hypertrophy through ferroptosis in a selective autophagy crosstalk manner DOI Creative Commons
Tianyu Li, Mengqi Sun,

Qinglin Sun

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103158 - 103158

Published: April 12, 2024

Exposure to PM2.5 is correlated with cardiac remodeling, of which hypertrophy one the main clinical manifestations. Ferroptosis plays an important role in hypertrophy. However, potential mechanism PM2.5-induced through ferroptosis remains unclear. This study aimed explore molecular caused by and intervention MitoQ involved this process. The results showed that could induce dysfunction mice. Meanwhile, characteristics were observed, such as iron homeostasis imbalance, lipid peroxidation, mitochondrial damage abnormal expression key molecules. treatment effectively mitigate these alternations. After treating human cardiomyocyte AC16 PM2.5, activator (Erastin) inhibitor (Fer-1), it was found promote ferritinophagy lead well accumulation intracellular labile iron. Subsequently, mitophagy activated provided additional source iron, enhancing sensitivity cells ferroptosis. Furthermore, Fer-1 alleviated cytotoxicity overload cytoplasm mitochondria cells. It worth noting during process ferroptosis, metabolism mediated activation a temporal order. In addition, NCOA4 knockdown reversed imbalance peroxidation thereby alleviating summary, our imbalance-mediated crosstalk played

Language: Английский

Citations

17
Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases DOI Creative Commons
Qi Feng, Yang Yang, Kaidi Ren

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(12), P. 3726 - 3743

Published: Jan. 1, 2023

Ferroptosis is an iron-dependent programmed cell death pattern that characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support the imbalance of homeostasis disturbance metabolism contribute to tissue or organ injury in various kidney diseases triggering ferroptosis. At present, key regulators complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role initiation progression has not fully revealed. Herein, we aim discuss features, ferroptosis, explore emerging roles organelles gather pharmacological progress, systematically summarize most recent discoveries about crosstalk between diseases, including renal carcinoma (RCC), acute (AKI), diabetic disease (DKD), autosomal dominant polycystic (ADPKD), fibrosis, lupus nephritis (LN) IgA nephropathy. We further conclude potential therapeutic strategies targeting for prevention treatment hope this work will provide insight study pathogenesis kidney-related diseases.

Language: Английский

Citations

36
Fucoxanthin alleviated myocardial ischemia and reperfusion injury through inhibition of ferroptosis via the NRF2 signaling pathway DOI

Jing Yan,

Zehua Li,

Yu Liang

et al.

Food & Function, Journal Year: 2023, Volume and Issue: 14(22), P. 10052 - 10068

Published: Jan. 1, 2023

Background: Myocardial ischemia and reperfusion injury (MIRI) is a severe complication of revascularization therapy in patients with myocardial infarction. Therefore, there an urgent requirement to find more therapeutic solutions for MIRI. Recently, ferroptosis, which characterized by lipid peroxidation, was considered critical contributor Fucoxanthin (FX), natural antioxidant carotenoid, abundant brown seaweed, exerts protective effects under various pathological conditions. However, whether FX alleviates MIRI unclear. This study aims clarify the on Methods: Mice left anterior descending artery ligation were used as vivo models. Neonatal rat cardiomyocytes (NRCs) induced hypoxia vitro TTC-Evans blue staining performed validate infarction size. Transmission electron microscopy employed detect mitochondrial cardiomyocytes. In addition, 4 weeks after MIRI, echocardiography measure cardiac function; fluorescent probes western blots ferroptosis. Results: showed that reduced size ameliorated MIRI-induced myofibril loss mitochondrion shrinkage. Furthermore, improved LVEF LVFS inhibited hypertrophy fibrosis mice study, calcein AM/PI TUNEL cell death caused treatment. DCFH-DA MitoSOX indicated cellular reactive oxygen species (ROS). Moreover, C11-BODIPY 581/591 staining, ferro-orange MDA assay, Fe2+ 4-hydroxynonenal enzyme-linked immunosorbent blot results revealed ferroptosis vivo, inhibiting ROS release, well modulating hallmark FTH, TFRC, GPX4 expression. Additionally, eliminated NRF2 inhibitor brusatol, observed from blotting, indicating exerted cardio-protective through pathway. Conclusion: Our alleviated inhibition via signaling

Language: Английский

Citations

29
Mitochondria-mediated Ferroptosis in Diseases Therapy: From Molecular Mechanisms to Implications DOI Creative Commons
Fuhai Feng, Shasha He, Xiaoling Li

et al.

Aging and Disease, Journal Year: 2023, Volume and Issue: 15(2), P. 714 - 714

Published: Aug. 2, 2023

Ferroptosis, a type of cell death involving iron and lipid peroxidation, has been found to be closely associated with the development many diseases. Mitochondria are vital components eukaryotic cells, serving important functions in energy production, cellular metabolism, apoptosis regulation. Presently, precise relationship between mitochondria ferroptosis remains unclear. In this study, we aim systematically elucidate mechanisms via which regulate from multiple perspectives provide novel insights into mitochondrial ferroptosis. Additionally, present comprehensive overview how contribute different conditions, including cancer, cardiovascular disease, inflammatory DNA depletion syndrome, coronavirus pneumonia. Gaining understanding involvement could lead more effective approaches for both basic biology studies medical treatments.

Language: Английский

Citations

27
Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia DOI Creative Commons
Hiroki Akiyama, Bing Z. Carter, Michael Andreeff

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1128 - 1128

Published: April 11, 2023

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved the regulation are complex and highly dependent on context. Therefore, comprehensive understanding its execution protection machinery each tumor type necessary for implementation this unique to target individual Since most current based solid cancer studies, knowledge with regard leukemia largely lacking. In review, we summarize ferroptosis-regulating respect metabolism phospholipids iron well major anti-oxidative pathways protect cells from ferroptosis. We also highlight diverse impact p53, master regulator cellular metabolic processes, Lastly, discuss recent studies provide future perspective development promising anti-leukemia therapies implementing induction.

Language: Английский

Citations

24
Trastuzumab-induced cardiomyopathy via ferroptosis-mediated mitochondrial dysfunction DOI Creative Commons
Ting Ye, Wei Yang,

Tielei Gao

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 206, P. 143 - 161

Published: June 30, 2023

Trastuzumab (TRZ) is a first-line chemotherapeutic agent for HER-2 (ErbB2)-positive breast cancer. Unfortunately, its clinical use limited due to cardiotoxicity, referred as TRZ-induced cardiotoxicity (TIC). However, the exact molecular mechanisms underlying development of TIC remain unclear. Iron and lipid metabolism redox reactions participate in ferroptosis. Here, we show that ferroptosis-mediated mitochondrial dysfunction involved vivo vitro. We first established models with BALB/c mice or neonatal rat cardiomyocytes confirmed cardiomyopathy echocardiography inhibition cell viability counting kit-8 examination, respectively. showed TRZ downregulated glutathione peroxidase 4 (GPx4) elevated peroxidation by-products, 4-hydroxynonenal (4-HNE) malondialdehyde (MDA), by inactivating ErbB2/PI3K/AKT/Nrf2 signalling pathway. Additionally, upregulated 4-HNE binds voltage-dependent anion channel 1 (VDAC1), increases VDAC1 oligomerization, subsequently induces dysfunction, evidenced permeability transition pore (mPTP) opening decreased membrane potential (MMP) ATP levels. Concomitantly, affected levels GSH/GSSG iron ions stability mitoGPx4. Ferroptosis inhibitors, such ferrostatin-1 (Fer-1) chelator deferoxamine (DFO), ameliorate cardiomyopathy. Overexpression mitoGPx4 also suppressed prevented Our study strongly suggests targeting cardioprotective strategy.

Language: Английский

Citations

24
Molecular Mechanisms and Therapeutic Targeting of Ferroptosis in Doxorubicin-Induced Cardiotoxicity DOI Creative Commons
Lin Wu, Yingmei Zhang, Guizhen Wang

et al.

JACC Basic to Translational Science, Journal Year: 2024, Volume and Issue: 9(6), P. 811 - 826

Published: Jan. 3, 2024

Ferroptosis, an iron-dependent form of regulated cell death, has received increasing attention for its pathophysiologic contribution to the onset and development doxorubicin-induced cardiotoxicity. Moreover, modulation ferroptosis with specific inhibitors may provide new therapeutic opportunities Here, we will review molecular mechanisms promise targeting in

Language: Английский

Citations

15
Polyacrylic Acid‐Coated Selenium‐Doped Carbon Dots Inhibit Ferroptosis to Alleviate Chemotherapy‐Associated Acute Kidney Injury DOI Creative Commons
Jiahuan Li, Chengcheng Fu,

Baoli Feng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(28)

Published: April 30, 2024

Abstract Cisplatin‐associated acute kidney injury (AKI) is a severe clinical syndrome that significantly restricts the chemotherapeutic application of cisplatin in cancer patients. Ferroptosis, newly characterized programmed cell death driven by lethal accumulation lipid peroxidation, widely reported to be involved pathogenesis cisplatin‐associated AKI. Targeted inhibition ferroptosis holds great promise for developing novel therapeutics alleviate Unfortunately, current inhibitors possess low bioavailability or perform non‐specific body, making them inefficient alleviating AKI inadvertently reducing anti‐tumor efficacy cisplatin, thus not suitable application. In this study, selenium nanomaterial, polyacrylic acid‐coated selenium‐doped carbon dots (SeCD), rationally developed. SeCD exhibits high biocompatibility and specifically accumulates kidney. Administration effectively scavenges broad‐spectrum reactive oxygen species facilitates GPX4 expression releasing selenium, resulting strong mitigation renal tubular epithelial cells substantial alleviation AKI, without compromising cisplatin. This study highlights promising therapeutic approach prevention patients undergoing chemotherapy.

Language: Английский

Citations

15