Cross Talk Between Ferroptosis and Cerebral Ischemia

She, Xu; Liu, Bin; Tian, Haibin; Tang, Biao

doi:10.3389/fnins.2020.00776

Cited by 55 publications

(43 citation statements)

References 76 publications

(121 reference statements)

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“…Necroptosis, an alternative form of programmed necrosis, is regulated by receptor-interacting protein (RIP) 1 activation and by RIP3 and mixed-lineage kinase domain-like (MLKL) phosphorylation via inhibition of caspase-8. Emerging studies have reported that ferroptosis and necroptosis both induce and aggravate brain tissue damage following the onset and development of cerebral ischemia and cerebral ischemia/reperfusion injury (CIRI) [4][5][6][7][8]. Regarding therapy, tissue plasminogen activator (t-PA), the only thrombolytic drug approved by the Food and Drug Administration for ischemic stroke treatment, dissolves blood clots by activating a proteolytic enzyme [8].…”

Section: Introductionmentioning

confidence: 99%

Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Zhou

Liao

Mei

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent accumulation of lipid hydroperoxides to lethal levels. Necroptosis, an alternative form of programmed necrosis, is regulated by receptor-interacting protein (RIP) 1 activation and by RIP3 and mixed-lineage kinase domain-like (MLKL) phosphorylation. Ferroptosis and necroptosis both play important roles in the pathological progress in ischemic stroke, which is a complex brain disease regulated by several cell death pathways. In the past few years, increasing evidence has suggested that the crosstalk occurs between necroptosis and ferroptosis in ischemic stroke. However, the potential links between ferroptosis and necroptosis in ischemic stroke have not been elucidated yet. Hence, in this review, we overview and analyze the mechanism underlying the crosstalk between necroptosis and ferroptosis in ischemic stroke. And we find that iron overload, one mechanism of ferroptosis, leads to mitochondrial permeability transition pore (MPTP) opening, which aggravates RIP1 phosphorylation and contributes to necroptosis. In addition, heat shock protein 90 (HSP90) induces necroptosis and ferroptosis by promoting RIP1 phosphorylation and suppressing glutathione peroxidase 4 (GPX4) activation. In this work, we try to deliver a new perspective in the exploration of novel therapeutic targets for the treatment of ischemic stroke.

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Section: Introductionmentioning

confidence: 99%

Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Zhou

Liao

Mei

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…That's why not all cells are susceptible to the same extend. The ferroptosis is reported as one of the fundamental forms of cell death in many neurological diseases [103], including Alzheimer's disease or Parkinson's disease [104], and Cerebral Ischemia [105]. The susceptibility of neural cells to ferroptosis, we explain the following way in the context of our research.…”

Section: Lipid Oxidation and Pore Formation Beyond Electroporationmentioning

confidence: 93%

On the permeability of cell membranes subjected to lipid oxidation

Wiczew

Szulc

Tarek

2020

Preprint

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The formation of transient hydrophilic pores in their membranes is a well-recognized mechanism of permeabilization of cells exposed to high-intensity electric pulses. However, the formation of such pores alone is not able to explain all aspects of the so-called electroporation phenomenon. In particular, the reasons for the sustained permeability of cell membranes, which persist long after the pulses' application, remain elusive: The complete resealing of the cell membranes takes indeed orders of magnitude longer than the time of electropore closure as reported from molecular modelling investigations. A possible alternative mechanism to explain the observed long-lived permeability of cell membranes, lipid peroxidation, has been previously suggested but the theoretical investigations of membrane lesions, containing excess amounts of hydroperoxides, have shown that the conductivities of such lesions were not high enough to reasonably explain the entire range of experimental measurements. Here, we expand on these studies and investigate the permeability of cell membrane lesions that underwent secondary oxidation. Molecular dynamics simulations and free energy calculations on lipid bilayer in different states show that such lesions provide a better model for post-pulsed permeable and conductive electropermeabilized cells. Furthermore, the results of the article are further discussed in the context of a type of cell death - ferroptosis, which is associated with lipid oxidation.

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“…In neurology, ferroptosis has been confirmed to participate in intracerebral hemorrhage, subarachnoid hemorrhage, Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease [ 14 – 18 ]. Preliminary evidence reveals that ferroptosis deteriorates ischemia-induced brain damage, while the administration of ferrostatin-1 (an inhibitor of ferroptosis) can effectively reverse induced damage [ 19 , 20 ]. Recently, increasing studies have focused on finding biomarkers of ferroptosis in multiple levels, including morphology, biochemistry, protein, and gene [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of a ferroptosis-related gene pair biomarker with immune infiltration landscapes in ischemic stroke: a bioinformatics-based comprehensive study

et al. 2022

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Background Ischemic stroke (IS) is a principal contributor to long-term disability in adults. A new cell death mediated by iron is ferroptosis, characterized by lethal aggregation of lipid peroxidation. However, a paucity of ferroptosis-related biomarkers early identify IS until now. This study investigated potential ferroptosis-related gene pair biomarkers in IS and explored their roles in immune infiltration. Results In total, we identified 6 differentially expressed ferroptosis-related genes (DEFRGs) in the metadata cohort. Of these genes, 4 DEFRGs were incorporated into the competitive endogenous RNA (ceRNA) network, including 78 lncRNA-miRNA and 16 miRNA-mRNA interactions. Based on relative expression values of DEFRGs, we constructed gene pairs. An integrated scheme consisting of machine learning algorithms, ceRNA network, and gene pair was proposed to screen the key DEFRG biomarkers. The receiver operating characteristic (ROC) curve witnessed that the diagnostic performance of DEFRG pair CDKN1A/JUN was superior to that of single gene. Moreover, the CIBERSORT algorithm exhibited immune infiltration landscapes: plasma cells, resting NK cells, and resting mast cells infiltrated less in IS samples than controls. Spearman correlation analysis confirmed a significant correlation between plasma cells and CDKN1A/JUN (CDKN1A: r = − 0.503, P < 0.001, JUN: r = − 0.330, P = 0.025). Conclusions Our findings suggested that CDKN1A/JUN could be a robust and promising gene-pair diagnostic biomarker for IS, regulating ferroptosis during IS progression via C9orf106/C9orf139-miR-22-3p-CDKN1A and GAS5-miR-139-5p/miR-429-JUN axes. Meanwhile, plasma cells might exert a vital interplay in IS immune microenvironment, providing an innovative insight for IS therapeutic target.

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Cross Talk Between Ferroptosis and Cerebral Ischemia

Cited by 55 publications

References 76 publications

Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

On the permeability of cell membranes subjected to lipid oxidation

Identification of a ferroptosis-related gene pair biomarker with immune infiltration landscapes in ischemic stroke: a bioinformatics-based comprehensive study

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