Dimethyl fumarate protects against hepatic ischemia-reperfusion injury by alleviating ferroptosis via the NRF2/SLC7A11/HO-1 axis

Qi, Debin; Chen, Peng; Bao, Haili; Zhang, Lei; Sun, Keyan; Song, Shaohua; Li, Tao

doi:10.1080/15384101.2022.2155016

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…In addition to HIFs, NRF2, the master regulator of oxidative stress signaling, also plays an important role in hypoxia-induced ferroptosis. Many studies reported that NRF mediates the regulation of ferroptosis induced by hypoxia or H/R [ 124 , 125 , 128 , 138 ], while another group of studies reported that targeting NRF2 could inhibit hypoxia-or H/R-induced ferroptosis [ 149 , 160 , 161 , 162 , 163 , 164 , 165 , 166 ].…”

Section: Discussionmentioning

confidence: 99%

“…From understanding the mechanism involved in the inhibition of ferroptosis caused by hypoxia, avoiding the ferroptosis inhibition caused by hypoxia could be a new strategy for treating tumors with ferroptosis inducers [ 180 , 181 ]. Considering that ferroptosis is the major reason for IRI, many drugs have been developed to inhibit hypoxia-induced ferroptosis based on its mechanism [ 129 , 140 , 141 , 150 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ]. Intriguingly, hypoxia is a symptom of the Coronavirus Disease-2019 (COVID-19); HIF-1α plays an important role in the early phase of SAR-CoV-2 infection and is also associated with secondary organ damage [ 182 , 183 ].…”

Section: Discussionmentioning

confidence: 99%

“…It was also reported that icariin and irisin protect against myocardial and lung injury, respectively, by suppressing H/R-induced ferroptosis of cardiomyocytes and lung epithelial cells via activating Nrf2/HO-1 signaling [ 161 , 162 ]. Additionally, dimethyl fumarate, a therapeutic agent for relapsing-remitting multiple sclerosis, inhibits H/R-induced ferroptosis in alpha mouse liver cells and a mouse liver IRI model by activating NRF2 pathway [ 163 ]. Melatonin, an antioxidant that regulates the sleep-wake cycle, was reported to inhibit RSL3-, erastin-, or H/R-induced ferroptosis through modulating NRF2, AKT, and GPX4, in hypoxic-ischemic brain damage, as well as through upregulating NRF2 and downregulating SLC7A11 in mouse tubular epithelial cells and a mouse acute kidney injury (AKI) model [ 164 , 165 ].…”

Section: The Mechanism and Regulation Of Ferroptosis Modulated By Hyp...mentioning

confidence: 99%

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Ferroptosis Regulated by Hypoxia in Cells

Zheng

Liang

Zhang

2023

Cells

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Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which is associated with many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, and immunologically distinct from other regulated cell death forms. Ferroptosis is regulated by iron metabolism, lipid metabolism, anti-oxidant defense systems, as well as various signal pathways. Hypoxia, which is found in a group of physiological and pathological conditions, can affect multiple cellular functions by activation of the hypoxia-inducible factor (HIF) signaling and other mechanisms. Emerging evidence demonstrated that hypoxia regulates ferroptosis in certain cell types and conditions. In this review, we summarize the basic mechanisms and regulations of ferroptosis and hypoxia, as well as the regulation of ferroptosis by hypoxia in physiological and pathological conditions, which may contribute to the numerous diseases therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The Mechanism and Regulation Of Ferroptosis Modulated By Hyp...mentioning

confidence: 99%

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Ferroptosis Regulated by Hypoxia in Cells

Zheng

Liang

Zhang

2023

Cells

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“…Neutrophil membrane-coated taurine nanoparticles increased the expression of SLC7A11 and GPX4, and decreased the expression of Ptgs2, suggesting that nano-taurine has a targeted therapeutic effect on hepatic I/R injury by inhibiting inflammation, oxidative stress and ferroptosis [ 417 ]. Dimethyl fumarate (DMF), a therapeutic agent utilized in the treatment of relapsing–remitting multiple sclerosis, demonstrates inhibitory effects on ferroptosis through activation of the NRF2/SLC7A11/HO-1 axis, thereby conferring protection against hepatic I/R injury [ 418 ]. Although the relationship between hepatic I/R injury and ferroptosis has been confirmed, the development and application of therapies and drugs targeting ferroptosis are still limited.…”

Section: Ferroptosis In Pathologiesmentioning

confidence: 99%

The mechanism of ferroptosis and its related diseases

Feng,

Tang,

Wang

et al. 2023

Mol Biomed

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Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.

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“…In addition, DMF inhibits the migration of immune cells across brain endothelial cells [ 26 ]. DMF has shown potential favorable effects in a range of diseases, such as hepatic ischemia-reperfusion injury [ 27 ], lymphoma [ 28 , 29 ], and inflammatory bowel disorders [ 30 ]. This medicine was also approved for the treatment of multiple sclerosis and psoriasis in the clinic [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing

Zhu,

Li,

Peng

et al. 2024

J Neuroinflammation

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Background Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. Methods To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. Results Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. Conclusions DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.

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Dimethyl fumarate protects against hepatic ischemia-reperfusion injury by alleviating ferroptosis via the NRF2/SLC7A11/HO-1 axis

Cited by 19 publications

References 32 publications

Ferroptosis Regulated by Hypoxia in Cells

Ferroptosis Regulated by Hypoxia in Cells

The mechanism of ferroptosis and its related diseases

Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing

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