Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion

Xu, Xiujian; Zhang, Liang; Ye, Xinchun; Qi, Hao; Zhang, Tao; Cui, Guiyun; Yu, Ming

doi:10.1007/s00011-017-1095-6

Cited by 102 publications

(63 citation statements)

References 37 publications

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“…It is well known that the distribution and degradation of Nrf2 are regulated by its endogenous inhibitor Keap1 [46]. Keap1 is a homo-dimer with two canonical domains: one binds to Nrf2 and the other binds to E3 ubiquitin ligase complex, which keeps Nrf2 in the cytoplasm and promotes its degradation [19]. To determine the reason for increased nuclear accumulation of Nrf2 after I/R, the changes of Keap1 were investigated.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to scavenging ROS directly, the activation of Nrf2 and the expression of its downstream genes may have protective effects against I/R damage, as validated by emerging evidence [18,19]. As one of the master regulators for defending against oxidative stress, Nrf2 binds to the antioxidant response element (ARE) in the nucleus and promotes a series of antioxidation gene expression [20].…”

Section: Introductionmentioning

confidence: 99%

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Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway

et al. 2018

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“…These beneficial results have also been validated in vitro; in oxygen-glucose deprivation/reperfusion (oGdr)-activated BV2 microglia, nrf2 was observed to be activated and dissociated from the repressor protein, Kelch ecH-associating protein 1. This facilitated its translocation from the cytoplasm to the nucleus, where it bound to the antioxidant response element (ARE) and induced the expression of downstream genes, such as NADPH quinone oxidoreductase and heme oxygenase 1, which scavenge ROS and nitric oxide (7,68,77). Additionally, the activation of Nrf2 was identified to decrease ROS, NOD like receptor family pyrin domain containing 3 (nlrP3) and il-1β expression levels in BV2 microglia (7).…”

Section: Nrfmentioning

confidence: 99%

“…This facilitated its translocation from the cytoplasm to the nucleus, where it bound to the antioxidant response element (ARE) and induced the expression of downstream genes, such as NADPH quinone oxidoreductase and heme oxygenase 1, which scavenge ROS and nitric oxide (7,68,77). Additionally, the activation of Nrf2 was identified to decrease ROS, NOD like receptor family pyrin domain containing 3 (nlrP3) and il-1β expression levels in BV2 microglia (7). However, despite the evident protective role of nrf2, further studies are required to elucidate whether this transcription factor and its signaling pathways may regulate M2 microglia polarization and function following ischemic stroke.…”

Section: Nrfmentioning

confidence: 99%

“…currently, intravenous thrombolysis and mechanical thrombectomy are the only effective means of treating ischemic stroke (5,6); however, these treatment options are limited by the short-recommended treatment window (6). in addition, a series of reperfusion injuries may occur following ischemic reperfusion (6,7); in particular, inflammation and oxidative stress are the main causes of reperfusion injuries, and the latter can induce the former (6)(7)(8)(9). an increasing amount of evidence has demonstrated that continuous neuroinflammation can damage neurons and the blood-brain barrier (BBB) during the process of cerebral infarction, and this in turn results in tissue destruction and worsens the functional outcome (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Modulators of microglia activation and polarization in ischemic stroke (Review)

et al. 2020

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ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. as the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. in response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. it has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. in addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. Contents 1. introduction 2. Microglia 3. Modulatory mechanisms of microglia polarization 4. autophagy 5. conclusions

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Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

Shen

Lou

et al. 2023

The Anatomical Record

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Inflammatory injury following ischemia‐reperfusion (I/R) severely limits the efficacy of stroke treatment. Edaravone dexborneol (C.EDA) has been shown to reduce inflammation following a cerebral hemorrhage. However, the precise anti‐inflammatory mechanism of C.EDA is unknown. In this study, we investigated whether C.EDA provides neuroprotection after I/R in rats, as well as the potential mechanisms involved. A middle cerebral artery occlusion/reperfusion (I/R) model was created using Sprague‐Dawley rats. The blood flow of the central cerebral artery was monitored by a laser speckle imaging system. The neurological score was used to assess behavioral improvement. Cerebral infarction volume was measured by TTC staining. And the integrity of the blood–brain barrier was detected by Evan's blue staining. The expression of the nuclear factor kappa‐B (NF‐κB)/ the NOD‐like receptor protein (NLRP3) inflammasome signal pathway and microglia polarization were detected by immunofluorescence and Western blotting. The cerebral blood flow ratio indicates that the cerebral I/R model was successfully established. After reperfusion for 72 h, the improvement of neurological scores, infarct volume reduction, and integrity of the blood–brain barrier was observed in I/R rats with C.EDA treatment. Meanwhile, the immunofluorescence result showed that the expression of iNOS, NLRP3, and NF‐κB protein was decreased and the level of Arg1 was increased. Western blot analysis showed that the expression of NF‐κB/NLRP3 signal pathway‐related protein was decreased. In conclusion, this study indicates that C.EDA alleviates I/R injury by blocking the activation of the NLRP3 inflammasome and regulating the polarization of M1/M2 microglia via the NF‐κB signal pathway.

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Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion

Abstract: We elucidated an inhibitory regulation of Nrf2/ARE pathway on ROS-induced NLRP3 inflammasome activation in BV2 microglial cells after OGDR exposure.

Cited by 102 publications

References 37 publications

Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway

Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway

Modulators of microglia activation and polarization in ischemic stroke (Review)

Edaravone dexborneol alleviates cerebral ischemia‐reperfusion injury through NF‐κB/NLRP3 signal pathway

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