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.

• Authors: Qian Liu, Yun Li, Lin Zhou, Yunzi Li, Pengfei Xu, Xiaoyun Liu, Qiushi Lv, Juanji Li, Hongquan Guo, Haodi Cai, Rui Sun, Xinfeng Liu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2018 Pg. 3541807 ( 2018) ISSN: 1942-0994 [Electronic] United States
• PMID: 29849883 (Publication Type: Guideline, Journal Article)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• Heat-Shock Proteins
• Hspa5 protein, mouse
• Transcription Factor RelA
• Proto-Oncogene Proteins c-akt
• Glucose
• Oxygen

Topics

• Animals
• Apoptosis (physiology)
• Cell Survival (physiology)
• Disease Models, Animal
• Endoplasmic Reticulum Chaperone BiP
• Glucose (deficiency, metabolism)
• Heat-Shock Proteins
• Mice
• Neural Stem Cells (metabolism, pathology)
• Oxygen (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Transcription Factor RelA (metabolism)
• Transfection