Biochemical and biophysical research communications, 2015-02, Vol.457 (3), p.391-397
2015
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- Autor(en) / Beteiligte
- Titel
- EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages
- Ist Teil von
- Biochemical and biophysical research communications, 2015-02, Vol.457 (3), p.391-397
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- In this study, we tested the potential role of astragaloside IV (AS-IV) against oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted significant neuroprotective effects against OGD/R by reducing reactive oxygen species (ROS) accumulation, thereby attenuating oxidative stress and neuronal cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40 phosphorylation, and its nuclear localization, as well as transcription of antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown of Nrf2 through lentiviral shRNAs prevented AS-IV-induced ARE genes transcription, and abolished its anti-oxidant and neuroprotective activities. Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR) in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS-IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages through activating of EGFR-Nrf2 signaling. •Pre-treatment of astragaloside IV (AS-IV) protects murine cortical neurons from OGD/R.•AS-IV activates Nrf2-ARE signaling in murine cortical neurons.•Nrf2 is required for AS-IV-mediated anti-oxidant and neuroprotective activities.•AS-IV stimulates HB-EGF release to trans-activate EGFR in murine cortical neurons.•EGFR mediates AS-IV-induced Nrf2 activation and neuroprotection against OGD/R.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2015.01.002Titel-ID: cdi_osti_scitechconnect_22458478
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Animals, ANTIOXIDANTS, Antioxidants - pharmacology, Astragaloside IV, BENZOQUINONES, BUILDUP, Cerebral Cortex - drug effects, Cerebral Cortex - injuries, Cerebral Cortex - metabolism, DEATH, Disease Models, Animal, Drugs, Chinese Herbal - pharmacology, EGFR, Gene Knockdown Techniques, GENES, GLUCOSE, GROWTH FACTORS, HEME, HEPARIN, IN VITRO, ISCHEMIA, Ischemia/reperfusion, Mice, NAD, NERVE CELLS, Neurons - drug effects, Neurons - metabolism, Neuroprotection, Neuroprotective Agents - pharmacology, NF-E2-Related Factor 2 - antagonists & inhibitors, NF-E2-Related Factor 2 - genetics, NF-E2-Related Factor 2 - metabolism, Nrf2, OXIDATION, OXYGEN, Primary Cell Culture, Reactive Oxygen Species - metabolism, Receptor, Epidermal Growth Factor - antagonists & inhibitors, Receptor, Epidermal Growth Factor - genetics, Receptor, Epidermal Growth Factor - metabolism, RECEPTORS, Reperfusion Injury - genetics, Reperfusion Injury - metabolism, Reperfusion Injury - prevention & control, RNA, Messenger - genetics, RNA, Messenger - metabolism, Saponins - pharmacology, SIGNALS, STRESSES, TRANSCRIPTION, Transcriptional Activation - drug effects, Triterpenes - pharmacology