Ruscogenin Alleviates Myocardial Ischemia-Induced Ferroptosis through the Activation of BCAT1/BCAT2 DOI Creative Commons
Fei Fu, Qiong Lai,

Jingui Hu

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 583 - 583

Published: March 18, 2022

Ruscogenin (RUS), a natural steroidal sapogenin, exerts various biological activities. However, its effectiveness for preventing myocardial ischemia (MI) and molecular mechanisms need further clarification. The model of MI mice oxygen-glucose deprivation-induced cardiomyocytes injury was performed. RUS significantly alleviated MI, as evidenced by decreased infarct size, ameliorated biochemical indicators cardiac pathological features, markedly inhibited ferroptosis means the up-regulation GPX4 down-regulation ACSL4 FLC. Simultaneously, notably mitigated cell oxidative stress, in vitro. Subsequently, HPLC-Q-TOF/MS-based metabolomics identified BCAT1/BCAT2 possible regulatory enzymes responsible cardioprotection RUS. Importantly, treatment increased expression BCAT1 BCAT2 MI. Furthermore, we found that or siRNA viability, promoted ferroptosis, Keap1 expression, induced Nrf2 HO-1 degradation cardiomyocytes. Conversely, overexpression activated Keap1/Nrf2/HO-1 pathway. Moreover, pathway whereas partially weakened protective effects RUS, suggesting might suppress through BCAT2. Overall, this study demonstrated could alleviate MI-induced activation exerted cardioprotective via BCAT1/BCAT2.

Language: Английский

Regulated cell death in myocardial ischemia–reperfusion injury DOI
Q. Xiang, Xin Yi,

Xue‐Hai Zhu

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 35(3), P. 219 - 234

Published: Nov. 17, 2023

Language: Английский

Citations

140
A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis DOI Creative Commons
Dominik C. Fuhrmann, Bernhard Brüne

Redox Biology, Journal Year: 2022, Volume and Issue: 54, P. 102365 - 102365

Published: June 10, 2022

Ferroptosis is an iron-dependent form of cell death, which triggered by disturbed membrane integrity due to overproduction lipid peroxides. Induction ferroptosis comprises several alterations, i.e. altered iron metabolism, response oxidative stress, or peroxide production. At the physiological level transcription, translation, and microRNAs add appearance and/or activity building blocks that negatively positively balance ferroptosis. contributes tissue damage in case of, e.g., brain heart injury but may be desirable overcome chemotherapy resistance. For a more complete picture, it crucial also consider cellular microenvironment, during inflammation tumor context dominated hypoxia. This graphical review visualizes basic mechanisms ferroptosis, categorizes general inducers inhibitors puts focus on microRNAs, homeostasis, hypoxia as regulatory components.

Language: Английский

Citations

75
The Mechanisms of Ferroptosis Under Hypoxia DOI Creative Commons
Xīn Gào, Wei Hu, Dianlun Qian

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3329 - 3341

Published: July 17, 2023

Abstract Ferroptosis is a new form of programmed cell death, which characterized by the iron-dependent accumulation lipid peroxidation and increase ROS, resulting in oxidative stress death. Iron, lipid, multiple signaling pathways precisely control occurrence implementation ferroptosis. The mainly include Nrf2/HO-1 pathway, p62/Keap1/Nrf2 pathway. Activating pathway inhibits promotes Furthermore, some factors also participate ferroptosis under hypoxia, such as HIF-1, NCOA4, DMT1. Meanwhile, related with hypoxia-related diseases, MIRI, cancers, AKI. Accordingly, appears to be therapeutic target for diseases.

Language: Английский

Citations

62
Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling DOI Creative Commons
Solveigh C. Koeberle, Anna P. Kipp,

Hermann Stuppner

et al.

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(3), P. 614 - 682

Published: Jan. 19, 2023

Abstract Ferroptosis is an iron‐dependent cell death program that characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions structural features of ferroptosis‐inducing compounds might therefore open door efficient pharmacological strategies against aggressive, metastatic, therapy‐resistant cancer. We here summarize mechanisms requirements small molecules target central players ferroptosis. Focus placed on (i) glutathione peroxidase (GPX) 4, only GPX isoenzyme detoxifies complex membrane‐bound hydroperoxides, (ii) cystine/glutamate antiporter system X c − for regeneration, (iii) redox‐protective transcription factor nuclear erythroid 2‐related (NRF2), (iv) GPX4 repression combination with induced heme degradation via oxygenase‐1. deduce common ferroptotic activity highlight challenges development. Moreover, we critically discuss potential natural products lead structures provide comprehensive overview structurally diverse biogenic bioinspired trigger iron oxidation, inhibition thioredoxin/thioredoxin reductase or less defined modes action.

Language: Английский

Citations

55
Ferroptosis in colorectal cancer: a future target? DOI
Hong Yan, Ronan Talty, Oladimeji Aladelokun

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 128(8), P. 1439 - 1451

Published: Jan. 26, 2023

Language: Английский

Citations

49
Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice DOI
Deshan Yao,

Liuxiang Bao,

Sichuan Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 221, P. 1 - 12

Published: May 9, 2024

Language: Английский

Citations

24
Cardiac Fibroblasts Promote Ferroptosis in Atrial Fibrillation by Secreting Exo-miR-23a-3p Targeting SLC7A11 DOI Creative Commons
Dishiwen Liu, Mei Yang,

Yajun Yao

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 31

Published: May 29, 2022

The exact mechanism of atrial fibrillation (AF) has been not well elucidated. Ferroptosis is an iron-dependent cell death due to excessive accumulation peroxidized polyunsaturated fatty acids. However, the molecular underlying AF and ferroptosis never reported. Here, we established rapid pacing model in vivo vitro investigate relationship between ferroptosis. In canine pacing, content malondialdehyde total ions tissue Pacing group was significantly increased exosome inhibitor GW4869 reduced ferroptosis, fibrosis, inflammation improved histological electrophysiological remodeling. h9c2 cells, expression antioxidative stress genes associated with presented sequential changes proteins involved such as FTH1, SLC7A11, GPX4 were gradually depleted. Furthermore, cardiac fibroblast-derived exosomes (CF-exos) exacerbated cells pretreated pacing-CF-exos alleviated injury cells. mechanism, our results demonstrated that highly expressed miR-23a-3p by informatics analysis experimental verification. Inhibitor-miR-23a-3p protected from accompanying upregulation SLC7A11. addition, SLC7A11 shown be target gene miR-23a-3p. conclusion, suggest CF-exos-miR-23a-3p may promote development a persistent direction could prevented intervening exosomal miRNAs reduce oxidative

Language: Английский

Citations

61
Resveratrol Attenuate Myocardial Injury by Inhibiting Ferroptosis Via Inducing KAT5/GPX4 in Myocardial Infarction DOI Creative Commons
Jing Liu, Mingming Zhang,

Chaoshi Qin

et al.

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

Published: May 24, 2022

Myocardial infarction (MI) is a coronary artery-related disease and ranks as the leading cause of sudden death globally. Resveratrol (Res) bioactive component has presented antioxidant, anti-inflammatory anti-microbial properties. However, effect Res on ferroptosis during MI progression remains elusive. Here, we aimed to explore function in regulation myocardial injury MI. We observed that treatment attenuated MI-related myocardium fibrosis rats. The expression collagen 1 α-SMA was induced rats, which could decrease expression. Treatment suppressed levels IL-6 IL-1β GSH were inhibited MDA, lipid ROS, Fe2+ reverse phenotypes. Meanwhile, GPX4 SLC7A11 reduced while rescue model. relieved oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. Importantly, repressed OGD-induced vitro. Mechanically, identified able enhance by inducing KAT5 confirmed alleviated ferroptosis. depletion or Thus, concluded inhibiting via KAT5/GPX4 infarction. Our finding provides new evidence potential therapeutic targeting

Language: Английский

Citations

53
Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction DOI Creative Commons
Sai Ma, Lili He,

Guorui Zhang

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2022, Volume and Issue: 395(8), P. 945 - 962

Published: April 27, 2022

Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due their clear cardiovascular benefits for heart failure with preserved ejection fraction (HFpEF) since there are no effective that may improve clinical outcomes these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, newly defined mechanism of iron-dependent non-apoptotic cell death during (HF). Here, proteomics, we demonstrated ferroptosis might be key in rat model high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment canagliflozin. Data available via ProteomeXchange identifier PXD029031. The evaluated levels acyl-CoA synthetase long-chain family member 4, glutathione peroxidase ferritin heavy chain 1, transferrin receptor, Ferroportin iron, glutathione, malondialdehyde, 4-hydroxy-trans-2-nonenal. These findings highlight fact targeting serve as cardioprotective strategy HFpEF prevention suggest canagliflozin exert partly mitigation ferroptosis.

Language: Английский

Citations

52
The critical role of ferritinophagy in human disease DOI Creative Commons
Mengzhen Liu,

Ni Kong,

Guangyu Zhang

et al.

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

Published: Sept. 8, 2022

Ferritinophagy is a type of autophagy mediated by nuclear receptor activator 4 (NCOA4), which plays role in inducing ferroptosis regulating iron homeostasis and producing reactive oxygen species cells. Under physiological conditions, ferritinophagy maintains the stability intracellular release free iron. Studies have demonstrated that necessary to induce ferroptosis; however, under pathological excessive results large quantities, leads lipid peroxidation iron-dependent cell death, known as ferroptosis. has become an area interest recent years. We here review mechanism its association with various diseases provide reference for future clinical scientific studies.

Language: Английский

Citations

41