GRP78 Promotes Neural Stem Cell Antiapoptosis and Survival in Response to Oxygen‐Glucose Deprivation (OGD)/Reoxygenation through PI3K/Akt, ERK1/2, and NF‐κB/p65 Pathways

Abstract

When brain injury happens, endogenous neural stem cells (NSCs) located in the adult subventricular zone (SVZ) and subgranular zone (SGZ) are attacked by ischemia/reperfusion to undergo cellular apoptosis and death before being induced to migrate to the lesion point and differentiate into mature neural cells for damaged cell replacement. Although promoting antiapoptosis and NSC survival are critical to neuroregeneration, the mechanism has yet been elucidated clearly. Here in this study, we established an in vitro oxygen-glucose deprivation (OGD)/reoxygenation model on NSCs and detected glucose-regulated protein 78 (GRP78) involved in apoptosis, while in the absence of GRP78 by siRNA transfection, OGD/reoxygenation triggered PI3K/Akt, ERK1/2, and NF-κB/p65 activation, and induced NSC apoptosis was attenuated. Further investigation, respectively, with the inhibitor of PI3K/Akt or ERK1/2 demonstrated a blockage on GRP78 upregulation, while the inhibition of NF-κB rarely affected GRP78 induction by OGD/reoxygenation. The results indicated the bidirectional regulations of GRP78-PI3K/Akt and GRP78-ERK1/2 and the one-way signalling transduction through GRP78 to NF-κB/p65 on NSC survival from OGD/reoxygenation. In conclusion, we found that GRP78 mediated the signalling cross talk through PI3K/Akt, ERK1/2, and NF-κB/p65, which leads to antiapoptosis and NSC survival from ischemic stroke. Our finding gives a new evidence of GRP78 in NSCs as well as a new piece of signalling mechanism elucidation to NSC survival from ischemic stroke.

Biochanin A Alleviates Cerebral Ischemia/Reperfusion Injury by Suppressing Endoplasmic Reticulum Stress-Induced Apoptosis and p38MAPK Signaling Pathway In Vivo and In Vitro

“…The GRP78 inducer BiP inducer X (BIX) can, consequently, suppress apoptosis in response to ER stress in vivo and in vitro (21). There is also prior evidence that GRP78 protects neural stem cells against OGD/R-induced cell death through the regulation of PI3K/Akt, ERK1/2, and NF-kB/p65 (22). In the present report, we found that biochanin A enhanced the expression of GRP78 in the context of cerebral I/R injury, thereby helping to restore ER homeostasis and support neuronal survival.…”

Overexpression of BRCA1 in Neural Stem Cells Enhances Cell Survival and Functional Recovery after Transplantation into Experimental Ischemic Stroke

“…NSCs were harvested from embryonic C57BL/6J mouse brain (E14) as previously described [14]. Briefly, cells were resuspended in a DMEM/F12 medium containing B27 (2%, Gibco, USA), EGF (20 ng/ml, BioLegend, USA), bFGF (20 ng/ml, BioLegend, USA), and ITSS (10 μ g/ml, Roche, Switzerland) and cultured in a cell incubator.…”

Neural stem cells-from quiescence to differentiation and potential clinical uses

“…2021 4 (1) 23-41 27 levels in NSCs (Cai et al, 2014). Moreover, after oxygen-glucose deprivation, glucose-regulated protein 78 exercises anti-apoptotic and proliferative effects through PI3K/Akt and ERK1/2 pathways (Liu et al, 2018). Phytochemicals, such as astragalosides (Chen et al, 2019;Sun et al, 2020) and musk ketone (Zhou et al, 2020), that were known for their beneficial post-stroke effects, decrease apoptosis and enhance proliferation by regulating EGFR/MAPK and PI3K/Akt signaling.…”