COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion

Xu, Yunfei; Liu, Ying; Li, Kexin; Yuan, Dejian; Yang, Shun Fa; Zhou, Lin; Zhao, Yao; Miao, Shuying; Lv, Caihong; Zhao, Jie

doi:10.1007/s12035-021-02706-1

Cited by 56 publications

(40 citation statements)

References 41 publications

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“…Inhibiting this process by enhancing the expression of GPX4, the main regulatory enzyme of ferroptosis, leads to reduced neuronal deficit after ischemia and reduced neuronal death (Guan et al, 2019(Guan et al, , 2021. These results are similar with other experimental studies, where ferroptosis inhibition by inhibiting its various pathways improved the neurological outcome and reduced the affected area in I/R injuries (Chen et al, 2021;Guo et al, 2021a;Wang et al, 2021b;Tuo et al, 2022;Xu et al, 2022).…”

Section: Ferroptosissupporting

confidence: 72%

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

et al. 2022

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Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the RNA-induced silencing complex either degrade or prevent target messenger RNAs from being translated and thus, can modulate the synthesis of target proteins. In the neurological field, miRNAs have been evaluated as potential regulators in brain development processes and pathological events. Following ischemic hypoxic stress, the cellular and molecular events initiated dysregulate different miRNAs, responsible for long-terming progression and extension of neuronal damage. Because of their ability to regulate the synthesis of target proteins, miRNAs emerge as a possible therapeutic strategy in limiting the neuronal damage following a cerebral ischemic event. This review aims to summarize the recent literature evidence of the miRNAs involved in signaling and modulating cerebral ischemia-reperfusion injuries, thus pointing their potential in limiting neuronal damage and repair mechanisms. An in-depth overview of the molecular pathways involved in ischemia reperfusion injury and the involvement of specific miRNAs, could provide future perspectives in the development of neuroprotective agents targeting these specific miRNAs.

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Section: Ferroptosissupporting

confidence: 72%

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

et al. 2022

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“…Despite being upregulated during ferroptosis, PTGS2 might not be involved in the production of lipid peroxidation. Whether PTGS2 affects the procedure of ferroptosis still needs further investigation ( 61 ). Second, PUFA oxidation occurs through Fenton reaction in a non-enzymatic way.…”

Section: Metabolism and Ferroptosismentioning

confidence: 99%

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

et al. 2022

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Ferroptosis, an iron-dependent form of programmed cell death marked by phospholipid peroxidation, is regulated by complex cellular metabolic pathways including lipid metabolism, iron balance, redox homeostasis, and mitochondrial activity. Initial research regarding the mechanism of ferroptosis mainly focused on the solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (GPX4) signal pathway. Recently, novel mechanisms of ferroptosis, independent of GPX4, have been discovered. Numerous pathologies associated with extensive lipid peroxidation, such as drug-resistant cancers, ischemic organ injuries, and neurodegenerative diseases, are driven by ferroptosis. Ferroptosis is a new therapeutic target for the intervention of IVDD. The role of ferroptosis in the modulation of intervertebral disc degeneration (IVDD) is a significant topic of interest. This is a novel research topic, and research on the mechanisms of IVDD and ferroptosis is ongoing. Herein, we aim to review and discuss the literature to explore the mechanisms of ferroptosis, the relationship between IVDD and ferroptosis, and the regulatory networks in the cells of the nucleus pulposus, annulus fibrosus, and cartilage endplate to provide references for future basic research and clinical translation for IVDD treatment.

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“…According to the principle that the degree value is greater than the median (degree = 6), 18 targets are considered to play an important role in the anti-inflammatory process of puerarin ( Table 1 ). Moreover, we found that some targets (such as Ahr , Ptgs2 and Alox15 ) highly correlated with ferroptosis [ 21 , 22 , 23 ]. The outcomes of the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis ( Figure 2 B, Supplement Table S2 ) suggested that the top 20 pathways could be roughly divided into inflammation-related, cancer-related and virus-related.…”

Section: Resultsmentioning

confidence: 99%

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

et al. 2022

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Puerarin is a natural flavonoid with significant anti-inflammatory effects. Recent studies have suggested that ferroptosis may involve puerarin countering inflammation. However, the mechanism of ferroptosis mediated by the anti-inflammatory process of puerarin has not been widely explored. Herein, puerarin at a concentration of 40 μM showed an anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages RAW264.7. The analysis of network pharmacology indicated that 51 common targets were enriched in 136 pathways, and most of the pathways were associated with ferroptosis. Subsequently, the analysis of metabolomics obtained 61 differential metabolites that were enriched in 30 metabolic pathways. Furthermore, integrated network pharmacology and metabolomics revealed that puerarin exerted an excellent effect on anti-inflammatory in RAW264.7 via regulating ferroptosis-related arachidonic acid metabolism, tryptophan metabolism, and glutathione metabolism pathways, and metabolites such as 20-hydroxyeicosatetraenoic acid (20-HETE), serotonin, kynurenine, oxidized glutathione (GSSG), gamma-glutamylcysteine and cysteinylglycine were involved. In addition, the possible active binding sites of the potential targeted proteins such as acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 15-lipoxygenase (ALOX15) and glutathione peroxidase 4 (GPX4) with puerarin were further revealed by molecular docking. Thus, we suggested that ferroptosis mediated the anti-inflammatory effects of puerarin in macrophages RAW264.7 induced by LPS.

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COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion

Cited by 56 publications

References 41 publications

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

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