Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway

Jiang, Ting; Cheng, Hui; Su, Jingjing; Wang, Xuncui; Wang, Qiaoxue; Chu, Jun; Li, Qinglin

doi:10.1016/j.tiv.2019.104715

Cited by 131 publications

(84 citation statements)

References 38 publications

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“…In contrast, 4P-PDOT and PD98059 treatment blocked the up-regulatory effect of Mel on p-ERK, whereas ML385 induced no changes. A previous study reported that gastrodin can ameliorate oxidative stress and ferroptosis caused by glutamate in HT-22 cells through the Nrf2/HO-1 signaling pathway (Jiang et al, 2020), and several reports have stated that Mel attenuates the oxidative stress and memory impairment associated with klotho deficiency through a signaling interaction between the MT2 receptor and Nrf2related antioxidant effects (Shin et al, 2015). In this context, our findings suggested that Mel activates the ERK signaling pathway through the MT2 receptor pathway, which in turn activates the expression of Nrf2 and downstream signaling molecules, inhibiting SD-induced ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

Wang

Cao

et al. 2021

Front. Pharmacol.

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Objectives: Memory decline caused by insufficient sleep is a critical public health issues and currently lacks effective treatments. This study objective was to explore alleviative effect of melatonin on sleep deprivation (SD)-induced deficiencies in learning and memory.Materials and Methods: A continuous 72 h SD mouse model, with or without melatonin or Fer-1 supplementation were established. The changes of cognitive function, iron homeostasis, lipid peroxidation and intracellular signal pathways in mice were detected by Morris water maze, antioxidant assay, immunohistochemistry, western blot, RT-PCR and Prussian blue staining. In vitro, we treated HT-22 cells with ferroptosis inducer (Erastin) to further explore the specific mechanism of melatonin in ferroptosis.Results: Mice subjected to SD had significantly elevated latency and path length to reach hidden platform, as well as a decrease in number of entries and time spent in the target zone when the hidden platform was removed (p < 0.05). Nevertheless, supplementation with ferroptosis inhibitor (Fer-1) mitigated the memory impairment associated with SD. Further evaluation revealed an up-regulation of intracellular iron accumulation, transferrin receptor 1 and divalent metal transporter 1 expression and ROS and MDA production, and a down-regulation of ferroportin and antioxidant enzyme (GPX4 and SOD) expression in SD mice. SD decreased expression of MT2 receptor rather than of MT1, and inhibited ERK/Nrf2 signaling activation in the hippocampus (p < 0.05). In contrast, the aforementioned SD-inductions were reversed by supplementation using 20 and 40 mg/kg melatonin in SD mice. In vitro, melatonin pretreatment reversed Erastin-induced ferroptosis, abnormalities in iron transporter protein and antioxidant enzyme expression and suppression of ERK/Nrf2 signaling in HT-22 cells, however this protective effect of melatonin was blocked by MT2-, ERK- and Nrf2-specific antagonists (p < 0.05).Conclusion: Our finding suggested SD may induce ferroptosis, in turn leading to cognitive deficits. Melatonin alleviated memory loss and hippocampal ferroptosis caused by acute SD through binding to the MT2 receptor to activate ERK/Nrf2 signaling.

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Section: Discussionmentioning

confidence: 99%

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

Wang

Cao

et al. 2021

Front. Pharmacol.

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“…Moreover, Nrf2 plays a protective role against oxidative stress through regulating antioxidative genes, such as NQO1 and heme oxygenase-1 (HO-1) [18]. Moreover, Jiang et al showed that Nrf2 regulates HO-1 protein transcription in glutamateinduced HT-22 cell ferroptosis [19]. Cheng et al indicated that cigarette smoke particle-phase extract mediated HO-1 and Nrf2 expression in human tracheal smooth muscle cells [20].…”

Section: Introductionmentioning

confidence: 99%

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways

et al. 2020

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Background: It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium, plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. Methods: The levels of IL-1 β, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells' apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. Results: In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 β, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress.

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“…Bilirubin pretreatment could increase the GPX4 expression after ferroptosis caused cell injury, indicating that bilirubin could counteract the ferroptosis-induced effects. The Nrf2/HO-1 signaling has a complex regulatory mechanism in oxidative stress disease (Yao et al, 2020a;Yao et al, 2020b) and has been reported to be involved in the protective effects against ferroptosis (Jiang et al, 2020). Our results demonstrated that both Nrf2 and HO-1 expression were significantly decreased while the cells exposed to the ferroptosis inducers, which could be offset by the ferroptosis inhibitors.…”

Section: Discussionmentioning

confidence: 54%

Bilirubin Protects Transplanted Islets by Targeting Ferroptosis

et al. 2020

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Islet transplantation is an attractive treatment for type 1 diabetic patients. However, transplanted islets suffered from considerable cell death due to inflammatory reactions and oxidative stress. Ferroptosis is a programmed death characterized by iron-dependent lipid peroxidation, which has been implicated in the islet loss and dysfunction. Our previous studies showed that bilirubin displayed protection effect for islets by inhibiting early inflammation and oxidative stress. However, whether bilirubin protects islets by targeting ferroptosis has not yet been elucidated. Here, the isolated islet was exposed to ferroptosis-inducing agents with or without bilirubin. Islet viability, insulin secretion, and oxidative stress levels were assessed. Subsequently, the pretreated islets were transplanted into the subrenal site of streptozotocin-induced diabetic mice. Bilirubin could significantly attenuate ferroptosis in isolated islets, along with reduced oxidative stress, elevated GPX4 expression and upregulation of Nrf2/HO-1. Experimental data also confirmed that bilirubin could chelate iron. In vivo graft study demonstrated that euglycemia was achieved in diabetic mice receiving bilirubin-pretreated islets within 24 hours, while the control islets required at least 7 days. Bilirubin could improve islet viability and function through inhibiting ferroptosis, which could be of clinic interest to apply bilirubin into the islet transplantation system.

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Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway

Cited by 131 publications

References 38 publications

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways

Bilirubin Protects Transplanted Islets by Targeting Ferroptosis

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