Circular RNA FEACR inhibits ferroptosis and alleviates myocardial ischemia/reperfusion injury by interacting with NAMPT DOI Creative Commons
Jie Ju, Xinmin Li,

Xuemei Zhao

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: June 27, 2023

Abstract Background Emerging research has reported that circular RNAs (circRNAs) play important roles in cardiac cell death after myocardial ischemia and reperfusion (I/R). Ferroptosis, a new form of discovered recent years, been proven to participate the regulation I/R. This study used circRNA sequencing explore key ferroptosis I/R mechanisms potential function. Methods We performed circRNAs differentially expressed quantitative polymerase chain reactions determine expression different tissues detect subcellular localization cardiomyocyte. Gain- loss-of-function experiments were aimed examine function cardiomyocyte tissue damage RNA pull-down was applied proteins interacting with circRNA. Results Here, we identified ferroptosis-associated (FEACR) an underlying regulatory role ferroptosis. FEACR overexpression suppressed I/R-induced infarction ameliorated inhibition induces cardiomyocytes inhibits hypoxia reoxygenation-induced Mechanistically, directly bound nicotinamide phosphoribosyltransferase (NAMPT) enhanced protein stability NAMPT, which increased NAMPT-dependent Sirtuin1 (Sirt1) expression, promoted transcriptional activity forkhead box O1 (FOXO1) by reducing FOXO1 acetylation levels. further upregulated transcription ferritin heavy 1 ( Fth1 ), suppressor, resulted Conclusions Our finding reveals FEACR-mediated NAMPT-Sirt1-FOXO1-FTH1 signaling axis participates protects heart against injury. Thus, its downstream factors could be novel targets for alleviating ferroptosis-related injury ischemic diseases.

Language: Английский

The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease DOI Open Access
Xuexian Fang, Hossein Ardehali, Junxia Min

et al.

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(1), P. 7 - 23

Published: July 4, 2022

Language: Английский

Citations

645
Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases DOI
Jun Ren, Yaguang Bi, James R. Sowers

et al.

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 18(7), P. 499 - 521

Published: Feb. 22, 2021

Language: Английский

Citations

491
Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury DOI Creative Commons
Ning Li, Wei Wang, Heng Zhou

et al.

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 160, P. 303 - 318

Published: Aug. 23, 2020

Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of regulated cell death (RCD), playing critical roles in organ injury targeting therapy cancers. Previous studies have demonstrated that ferroptosis participates the development cardiomyopathy including cardiac hypertrophy, diabetic doxorubicin-induced cardiotoxicity. However, role sepsis-induced remains unclear. This study aimed to explore underlying mechanism on lipopolysaccharide (LPS)-induced injury. Mice were injected with LPS (10 mg/kg) for 12 h generate experimental sepsis. Ferrostatin-1 (Fer-1) Dexrazoxane (DXZ) used suppress mice increased levels ferroptotic markers involving prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA) lipid ROS, apart from resulting obvious mitochondria damage, which alleviated by Fer-1 DXZ. In vitro experiments showed inhibited LPS-induced peroxidation H9c2 myofibroblasts while erastin sorafenib aggravated ferroptosis. Additionally, DXZ improved survival rate function Mechanistically, expression nuclear receptor coactivator 4 (NCOA4) level intracellular Fe2+ but decreased ferritin. NCOA4 could directly interact ferritin degrade it ferritinophagy-dependent manner, subsequently released great amount iron. Cytoplasmic further activated siderofexin (SFXN1) mitochondrial membrane, turn transported cytoplasmic into mitochondria, giving rise production ROS Based these findings, we concluded ferritinophagy-mediated one mechanisms contributing Targeting cardiomyocytes may be therapeutic strategy preventing sepsis future.

Language: Английский

Citations

490
Ferroptosis as a novel therapeutic target for cardiovascular disease DOI Creative Commons
Xiaoguang Wu, Yi Li,

Shuchen Zhang

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 11(7), P. 3052 - 3059

Published: Jan. 1, 2021

Cell death is an important component of the pathophysiology cardiovascular disease. An understanding how cardiomyocytes die, and why regeneration cells in heart limited, a critical area study. Ferroptosis form regulated cell that characterized by iron overload, leading to accumulation lethal levels lipid hydroperoxides. The metabolism iron, lipids, amino acids glutathione tightly controls initiation execution ferroptosis. Emerging evidence shows ferroptosis closely associated with occurrence progression various diseases. In recent years, has been found play roles cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, failure. This article reviews mechanisms which initiated controlled discusses as novel therapeutic target for

Language: Английский

Citations

441
Ferritinophagy and ferroptosis in the management of metabolic diseases DOI
Amir Ajoolabady,

Hamid Aslkhodapasandhokmabad,

Peter Libby

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2021, Volume and Issue: 32(7), P. 444 - 462

Published: May 15, 2021

Language: Английский

Citations

241
Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion DOI
Lijing Tang,

Yuan-Jing Zhou,

Xiao-Ming Xiong

et al.

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 162, P. 339 - 352

Published: Nov. 4, 2020

Language: Английский

Citations

222
GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment DOI
Yi Liu,

Yicong Wan,

Yi Jiang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188890 - 188890

Published: March 29, 2023

Language: Английский

Citations

220
Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus DOI Creative Commons
Wenxin Sha, Fei Hu, Xi Yang

et al.

Journal of Diabetes Research, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 10

Published: June 28, 2021

Ferroptosis is a novel form of nonapoptotic regulated cell death (RCD). It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes, especially glutathione peroxidase 4 (GPX4). RAS-selective lethal 3 (RSL3), erastin, and ferroptosis inducing 56 (FIN56) induce via different manners targeting GPX4 function. Acyl-CoA synthetase long-chain family (ACSL4), lysophosphatidylcholine acyltransferase (LPCAT3), lipoxygenases (LOXs) participate in the production peroxides. Heat shock protein B member 1 (HSPB1) nuclear receptor coactivator (NCOA4) regulate iron homeostasis preventing caused high concentration intracellular iron. ubiquitous our body as it exists both physiologic pathogenic processes. involved glucose-stimulated insulin secretion (GSIS) impairment arsenic-induced pancreatic damage pathogenesis diabetes. Moreover, iron-sulfur (Fe-S) cluster influence each other, causing mitochondrial accumulation, more reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, failure biosynthesis insulin, β-cells. In addition, also engages diabetic complications such myocardial ischemia cardiomyopathy (DCM). this review, we summarize mechanism its association with type 2 diabetes mellitus (T2DM).

Language: Английский

Citations

210
Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc-/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis DOI Open Access
Shujun Xu,

Bingxin Wu,

Biying Zhong

et al.

Bioengineered, Journal Year: 2021, Volume and Issue: 12(2), P. 10924 - 10934

Published: Oct. 26, 2021

Ferroptosis is an important form of myocardial cell death in ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has significant advantage improving MIRI. But the regulatory effect and mechanism NAR on ferroptosis MIRI have not been reported. After rats were given induced to (MI/R) injury, Tetrazolium chloride (TTC) staining was used detect infarction area rats, Hematoxylin-eosin (H&E) injury. The markers tissue inflammation detected by ELISA. Serum creatine kinase creatin (CPK), Lactate dehydrogenase (LDH), lipid peroxide (LPO) oxidative stress related levels measured. In addition, iron detection kits total Fe2+ cardiac tissues, western blot expression ferroptosis-related proteins nuclear factor-erythroid factor 2-related 2 (Nrf2) glutathione peroxidase 4 (GPX4). At cellular level, H9C2 cardiomyocytes hypoxia/reoxygenation (H/R), inducer Erastin administered viability, indicators, expressions Nrf2 GPX4, explore mechanisms involved. alleviated MI/R-induced pathological damage, peroxidation rats. adjusted NRF2 /System xc - /GPX4 axis improved ferroptosis. reversed protective H/R-induced cardiomyocytes. conclusion, can alleviate regulating Nrf2/System xc-/GPX4 inhibit

Language: Английский

Citations

205
Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis DOI Creative Commons
Ting Li, Ying Tan,

Shao Ouyang

et al.

Gene, Journal Year: 2021, Volume and Issue: 808, P. 145968 - 145968

Published: Sept. 14, 2021

Resveratrol (Res) is a polyphenol with variety of biological activities. However, whether Res can prevent myocardial ischemia-reperfusion (I/R) injury not yet known. This study aimed to investigate the protective effect on I/R and explore its potential mechanism. H9c2 cells were used for in vitro experiments oxygen-glucose deprivation/reoxygenation (OGD/R) model was established. Rats ligated perfused by left anterior descending branch or without (50 mg/kg·bw) 14 days.The higher level oxidative stress Fe2+ content observed OGD/R-induced than that normal cells. showed increased ferroptosis, mainly reducing expression glutathione peroxidase 4 (GPX4) ferritin heavy chain 1 (FTH1), but enhancing transferrin receptor (TfR1). Both vivo indicated reduced Fe2 + content. In addition, inhibited decreased TfR1 expression, expressions FTH1 GPX4 rats. Moreover, we found ferroptosis regulation ubiquity specific peptidase 19 (USP19)-Beclin1 autophagy. protects against via attenuating ferroptosis. could be agent prevention injury.

Language: Английский

Citations

161