Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Dong-Xue Zhang, Li-Min Zhang, Xiao-Chun Zhao, Wenbo Sun
ObjectiveErythropoietin (EPO)-induced activation of the EPO receptor (EPOR) against sevoflurane-induced neuronal apoptosis is an effective intervention, but the underlying mechanism is poorly understood. Previous studies have shown that alteration of the nuclear factor erythroid 2-related factor (Nrf2)/BTB-to-CNC homology 1 (Bach1) ratio by extracellular signal-related kinases (Erk) 1/2 ameliorates the oxidative stress which occurs in human macrophages. In this study, we determined whether or not EPO attenuates sevoflurane-induced neuronal apoptosis via the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.MethodsPrimary rat cortical neurons were exposed to 4% sevoflurane for 6h. Neuronal viability, injury, apoptosis, and oxidative stress were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), propidium iodide uptake (PI), malondialdehyde (MDA), and superoxide dismutase (SOD) assays. A real-time PCR assay was used to measure EPOR expression. Western blotting was used to assess Nrf2, Bach1, and heme oxygenase-1 (HO-1) expression.ResultsSevoflurane exposure increased cell apoptosis, injury, and MDA (P<0.05), but decreased cell viability and the Nrf2:Bach1 ratio (P<0.05), and down-regulated superoxide dismutase (SOD; P<0.05), while EPO partially rescued the neurotoxicity induced by sevoflurane (P<0.05). Inhibition of EPOR via EPO-specific monoclonal antibody or Erk1/2 phosphorylation via PD98059 reversed the protective effect of EPO (P<0.05).ConclusionThe neuroprotective effects of EPO against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involves the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.
http://ift.tt/2hXlKys
Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Παρασκευή 6 Ιανουαρίου 2017
Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway
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