Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure

Wang, Wei; Wu, Yanfen; Zhang, Guoliang; Fang, Haibo; Wang, Hongchao; Zang, Hongmin; Xie, Ting; Wang, Weiping

doi:10.1016/j.brainres.2013.12.004

Cited by 86 publications

(62 citation statements)

References 29 publications

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“…The transient activation of Nrf2-ARE pathway might be a response to the oxidative stress caused by SE [55], but SE-induced Nrf2 activation was not enough to protect neurons from oxidative damage, which underlay the defects in mesodopaminergic system, as well as the elevated LPO and MDA in SN-VTA and Hip of SE rats in the present studies. However, Nrf2-ARE pathway provides a potential target in controlling epileptic seizures [24, 55]. …”

Section: Discussionmentioning

confidence: 99%

“…Administration of Ptx to rats did not alter Nrf2 expression [64]. Evidences demonstrate that the protective role of Nrf2-ARE pathway is mediated by HO-1 and NQO-1 [24]. Compared with control rats or SE rats 24 hrs following Pc, we found that intranasal Ptx pretreatment to SE rats significantly increased the levels of Nrf2, followed by upregulation of HO-1 and NQO-1 at mRNA and protein levels in Ptx-pretreated SE rats, which suggested that intranasal administration of Ptx might increase the antioxidative capability of cells by enhancing the SE-induced transient activation of Nrf2.…”

Section: Discussionmentioning

confidence: 99%

“…The rats in each group were tested for visuospatial memory 24 hrs after the Pc injection using Morris water maze test as described previously [24]. The water maze included a circular water tank (180 cm in diameter, 80 cm high) that was partially filled with water (23 ± 1°C).…”

Section: Methodsmentioning

confidence: 99%

“…Disruption of Nrf2-antioxidant response elements (ARE) pathway results in an increased susceptibility to oxidative insults and other toxicants [21]. Activation of Nrf2-ARE pathway protects neurons against oxidative damage and excitotoxic damage [13, 22–24]. …”

Section: Introductionmentioning

confidence: 99%

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Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

Kang

Yan

Fang

et al. 2017

Oxidative Medicine and Cellular Longevity

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The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

Kang

Yan

Fang

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Previous studies have demonstrated that the expression of Nrf2 and HO-1 at protein and mRNA levels markedly increased in hippocampus of amygdala kindling rats [55, 56]. Moreover, activation of Nrf2-ARE signal pathway in hippocampus reduced the progression of amygdale kindling, and alleviated the cognitive impairment and oxidative stress induced by epileptic seizure [21, 57]. Thus, Nrf2-ARE pathway may bring great benefit to the brain damage after seizure.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via Nrf2/ARE Signaling

Shi

Wang

Teng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ginsenoside Rb1 (Rb1) has been reported to have varieties of neuroprotective effects. This study aimed to evaluate the effects of Rb1 on pentylenetetrazol (PTZ)-induced rat brain injury and Mg²⁺ free-induced neuron injury and analyzed the detailed molecular mechanisms in vivo and in vitro. Methods: Seizure duration and latency were measured in epilepsy kindled rat. The cognitive impairment was assessed by Morris water maze (MWM) test. Oxidative stress parameters, malondialdehyde (MDA) and glutathione (GSH) were measured by the 2-thiobarbituric acid methods and the DTNB-GSSG reductase recycling methods. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Neuronal apoptosis was measured by Annexin V-FITC and propidium iodide (PI) staining. Immunohistochemistry and immunofluorescence staining were performed to evaluate Nrf2 and HO-1 expressions. Expression of Nrf2, HO-1, Bcl-2, iNOS and LC3 were evaluated by western blot. Results: The PTZ-injured rats presented longer seizure duration and shorter seizure latency. Rb1 ameliorated these effects, as well as the cognitive deficits caused by PTZ exposure. Besides, Rb1 dose-dependently increased GSH levels, decreased MDA levels and alleviated neuronal damage in PTZ-treated rats. In vitro, Rb1 increased cell viability and decreased neuronal apoptosis in a dose-dependent manner under Mg²⁺ free condition. Moreover, in vivo and in vitro, Rb1 enhanced both the Nrf2 and HO-1 expressions. Furthermore, upregulation of the expression of Bcl-2 and downregulation of the expression of iNOS and LC3 were observed. However, knockdown of Nrf2 adversely affected the protective effects of Rb1 in epileptic hippocampal neurons. Conclusion: Rb1 conferred neuroprotective effects against PTZ-induced brain damage and Mg²⁺ free-induced neuron injury by activating Nrf2/ARE signaling.

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Deregulation of UCA1 expression may be involved in the development of chemoresistance to cisplatin in the treatment of non‐small‐cell lung cancer via regulating the signaling pathway of microRNA‐495/NRF2

Fan

et al. 2019

Journal Cellular Physiology

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Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide.As a platinum-based chemotherapeutic drug, cisplatin has been used for over 30 years in NSCLC treatment while its effects are diminished by drug resistance. Therefore, we aimed to study the potential role of UCA1 in the development of chemoresistance against cisplatin. Real-time polymerase chain reaction, western-blot analysis, and immunofluorescence were used to study the involvement of UCA1, miR-495, and NRF2 in chemoresistance against cisplatin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the effect of cisplatin on cell proliferation.Computational analysis and luciferase assay were carried out to explore the interaction among UCA1, miR-495, and NRF2. The cisplatin-R group exhibited lower levels of UCA1 and NRF2 expression but a higher level of miR-495 expression than the cisplatin-S group.The growth rate and half-maximal inhibitory concentration of cellular dipeptidyl peptidase (cisplatinum) of the cisplatin-R group were much higher than those in the cisplatin-S group.MiR-495 contained a complementary binding site of UCA1, and the luciferase activity of wild-type UCA1 was significantly reduced after the transfection of miR-495 mimics.MiR-495 directly targeted the 3′-untranslated region (3′-UTR) of NRF2, and the luciferase activity of wild-type NRF2 3′-UTR was evidently inhibited by miR-495 mimics. Finally, UCA1 and NRF2 expressions in the effective group were much lower than that in the ineffective group, along with a much higher level of miR-495 expression. We suggested for the first time that high expression of UCA1 contributed to the development of chemoresistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway.

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Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure

Cited by 86 publications

References 29 publications

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via Nrf2/ARE Signaling

Deregulation of UCA1 expression may be involved in the development of chemoresistance to cisplatin in the treatment of non‐small‐cell lung cancer via regulating the signaling pathway of microRNA‐495/NRF2

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