EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

Gu, Damin; Lu, Pei-Hua; Zhang, Ke; Wang, Xiang; Sun, Min; Guo-qian, Chen; Wang, Qiong

doi:10.1016/j.bbrc.2015.01.002

Cited by 80 publications

(44 citation statements)

References 22 publications

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“…Ischemia-reperfusion injury can be mimicked in cultured neuronal cells using oxygen glucose deprivation and re-oxygenation (OGDR) [3][4][5][6]. OGDR-induced neuronal cell death is mediated by oxidative stress [5,7], with sustained oxygen glucose deprivation (OGD; often over 1 h) disrupting mitochondrial functions.…”

Section: Introductionmentioning

confidence: 99%

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

Liu

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: New strategies are required to combat neuronal ischemia-reperfusion injuries. K6PC-5 is a novel sphingosine kinase 1 (SphK1) activator whose potential activity in neuronal cells has not yet been tested. Methods: Cell survival and necrosis were assessed with a Cell Counting Kit-8 assay and lactate dehydrogenase release assay, respectively. Mitochondrial depolarization was tested by a JC-1 dye assay. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling components were examined by quantitative real-timePCR and western blotting. Results: K6PC-5 protected SH-SY5Y neuronal cells and primary murine hippocampal neurons from oxygen glucose deprivation/re-oxygenation (OGDR). K6PC-5 activated SphK1, and SphK1 knockdown by targeted short hairpin RNA (shRNA) almost completely abolished K6PC-5-induced neuronal cell protection. Further work showed that K6PC-5 inhibited OGDR-induced programmed necrosis in neuronal cells. Importantly, K6PC-5 activated Nrf2 signaling, which is downstream of SphK1. Silencing of Nrf2 by targeted shRNA almost completely nullified K6PC-5-mediated neuronal cell protection against OGDR. Conclusion: K6PC-5 activates SphK1-Nrf2 signaling to protect neuronal cells from OGDR. K6PC-5 might be a promising neuroprotective strategy for ischemia-reperfusion injuries.

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Section: Introductionmentioning

confidence: 99%

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

Liu

Zhang

et al. 2018

Cell Physiol Biochem

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“…MHY1485 induced Nrf2 phosphorylation at Ser-40, which might cause it departure from its suppressor KEAP1 and subsequent stabilization [23, 24, 30, 31]. Indeed, Nrf2 expression was increased in MHY1485-treated cells.…”

Section: Discussionmentioning

confidence: 99%

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

Yang

Guo

et al. 2017

Oncotarget

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Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling.

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“…To examine the time dependency of OGD in SH-SY5Y cells, the cells were transiently exposed to OGD for different times (2,4,8,12, and 16 h) and then reoxygenated for 24 h and evaluated using the MTT and LDH assays. The MTT assay results showed that the viability of the OGD/R-exposed cells decreased in a time-dependent manner.…”

Section: Kc-gns Protect Human Neuronal Cells Against Ogd/r-stimulatedmentioning

confidence: 99%

“…Oxidative stress is due to an imbalance between pro-and antioxidants, and results in the excessive production of reactive oxygen species (ROS). 7,8 The brain has a highly developed endogenous antioxidant defense system to counteract the oxidative stress generated by neuronal damage. Antioxidant response element (ARE)-regulated Phase II detoxifying enzymes are the principal means by which neuronal cells protect themselves from excessive production of ROS.…”

Section: Introductionmentioning

confidence: 99%

Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

Park¹,

Chae²,

Park³

et al. 2017

IJN

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Recently, environment-friendly synthesis of gold nanoparticles (GNPs) has been extensively explored by biologists and chemists. However, significant research is still required to determine whether “eco-friendly” GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs), prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen–glucose deprivation/reoxygenation (OGD/R)-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet–visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm) and zeta potential (−20.3±0.04 mV) were determined by dynamic light scattering. The average diameter (41.07±3.05 nm) was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O–H, C–C, and C–N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p53, p21, and B-cell lymphoma 2-associated X protein were reversed by KC-GNs. The KC-GN-mediated protection against OGD/R-induced neurotoxicity was diminished by NRF2 and heme oxygenase-1 gene knockdowns. Collectively, these results suggested that KC-GNs exerted strong neuroprotective effects on human neuronal cells, which might be attributed to the attenuation of OGD/R-induced neuronal cell injury through the NRF2 signaling pathway.

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EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

Cited by 80 publications

References 22 publications

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

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EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

Cited by 80 publications

References 22 publications

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen&ndash;glucose deprivation and reoxygenation

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Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation