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Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.
Biomed Pharmacother. 2017 Mar; 87:332-341.BP

Abstract

OBJECTIVE

Erythropoietin (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.

METHODS

Primary 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.

RESULTS

Sevoflurane 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).

CONCLUSION

The neuroprotective effects of EPO against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involves the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.

Authors+Show Affiliations

Department of Gerontology, Cangzhou Central Hospital, Cangzhou, China.Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China. Electronic address: azai2010@126.com.Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28064106

Citation

Zhang, Dong-Xue, et al. "Neuroprotective Effects of Erythropoietin Against Sevoflurane-induced Neuronal Apoptosis in Primary Rat Cortical Neurons Involving the EPOR-Erk1/2-Nrf2/Bach1 Signal Pathway." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 87, 2017, pp. 332-341.
Zhang DX, Zhang LM, Zhao XC, et al. Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. Biomed Pharmacother. 2017;87:332-341.
Zhang, D. X., Zhang, L. M., Zhao, X. C., & Sun, W. (2017). Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 87, 332-341. https://doi.org/10.1016/j.biopha.2016.12.115
Zhang DX, et al. Neuroprotective Effects of Erythropoietin Against Sevoflurane-induced Neuronal Apoptosis in Primary Rat Cortical Neurons Involving the EPOR-Erk1/2-Nrf2/Bach1 Signal Pathway. Biomed Pharmacother. 2017;87:332-341. PubMed PMID: 28064106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. AU - Zhang,Dong-Xue, AU - Zhang,Li-Min, AU - Zhao,Xiao-Chun, AU - Sun,Wenbo, Y1 - 2017/01/05/ PY - 2016/11/08/received PY - 2016/12/15/revised PY - 2016/12/27/accepted PY - 2017/1/9/pubmed PY - 2017/2/22/medline PY - 2017/1/9/entrez KW - Erythropoietin KW - Extracellular signal-related kinases 1/2 KW - Neurotoxicity KW - Sevoflurane SP - 332 EP - 341 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 87 N2 - OBJECTIVE: Erythropoietin (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. METHODS: Primary 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. RESULTS: Sevoflurane 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). CONCLUSION: The neuroprotective effects of EPO against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involves the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28064106/Neuroprotective_effects_of_erythropoietin_against_sevoflurane_induced_neuronal_apoptosis_in_primary_rat_cortical_neurons_involving_the_EPOR_Erk1/2_Nrf2/Bach1_signal_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)32245-4 DB - PRIME DP - Unbound Medicine ER -