RGD Reference Report - Activation of the Nrf2/ARE signaling pathway by probucol contributes to inhibiting inflammation and neuronal apoptosis after spinal cord injury. - Rat Genome Database

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Activation of the Nrf2/ARE signaling pathway by probucol contributes to inhibiting inflammation and neuronal apoptosis after spinal cord injury.

Authors: Zhou, Zipeng  Liu, Chang  Chen, Shurui  Zhao, Haosen  Zhou, Kang  Wang, Wei  Yuan, Yajiang  Li, Zhuo  Guo, Yue  Shen, Zhaoliang  Mei, Xifan 
Citation: Zhou Z, etal., Oncotarget. 2017 Jul 8;8(32):52078-52093. doi: 10.18632/oncotarget.19107. eCollection 2017 Aug 8.
RGD ID: 13434916
Pubmed: PMID:28881715   (View Abstract at PubMed)
PMCID: PMC5581014   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.19107   (Journal Full-text)

The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process. We found that treatment of injured rats with probucol significantly increased levels of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), while levels of inflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased. This was associated with a reduction in neural cell apoptosis and promotion of nerve function recovery. These results demonstrate that the neuroprotective effects of probucol after SCI are mediated by activation of the Nrf2/ARE signaling pathway. These findings indicate that the anti-inflammatory effects of probucol represent a viable treatment for improving functional recovery following SCI.




  
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Evidence
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Original Reference(s)
NQO1HumanSpinal Cord Injuries  ISONqo1 (Rattus norvegicus)protein:increased expression:spinal cord (rat)RGD 
Nqo1RatSpinal Cord Injuries  IEP protein:increased expression:spinal cord (rat)RGD 
Nqo1MouseSpinal Cord Injuries  ISONqo1 (Rattus norvegicus)protein:increased expression:spinal cord (rat)RGD 


Genes (Rattus norvegicus)
Nqo1  (NAD(P)H quinone dehydrogenase 1)

Genes (Mus musculus)
Nqo1  (NAD(P)H dehydrogenase, quinone 1)

Genes (Homo sapiens)
NQO1  (NAD(P)H quinone dehydrogenase 1)