Oxygen–Glucose Deprivation (OGD) Modulates the Unfolded Protein Response (UPR) and Inflicts Autophagy in a PC12 Hypoxia Cell Line Model

Abstract

Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radical generation. The present study investigates the effect of hypoxia on the unfolded protein response of the cell (UPR), utilizing a 16-h oxygen-glucose deprivation protocol (OGD) in a PC12 cell line model. Expression of glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), key players of the UPR, was studied along with the expression of glucose-regulated protein 75 (GRP75), heat shock cognate 70 (HSC70), and glyceraldehyde 3-phosphate dehydrogenase, all with respect to the cell death mechanism(s). Cells subjected to OGD displayed upregulation of GRP78 and GRP94 and concurrent downregulation of GRP75. These findings were accompanied with minimal apoptotic cell death and induction of autophagy. The above observation warrants further investigation to elucidate whether autophagy acts as a pro-survival mechanism that upon severe and prolonged hypoxia acts as a concerted cell response leading to cell death. In our OGD model, hypoxia modulates UPR and induces autophagy.

Tissue kallikrein protects SH‐SY5Y neuronal cells against oxygen and glucose deprivation‐induced injury through bradykinin B2 receptor‐dependent regulation of autophagy induction

“…Discrepancies between apparently conflicting results among studies can be attributed to different experimental conditions, including the severity of the hypoxic insult, presence of reperfusion and timing of autophagy inducers or inhibitors (Vavilis et al . ). In our study, we established a 6 h OGD model without reperfusion, which resulted to about 55.1% cell survival, and administered TK during OGD.…”

RETRACTED ARTICLE: Lycium barbarum polysaccharide alleviates oxygen glucose deprivation-induced PC-12 cells damage by up-regulating miR-24

“…with 10% fetal bovine serum (FBS, Dojindo) was used to culture cells. The standard incubation conditions were 5% CO 2 , 37 C. The cell damage was induced by OGD for 16 h [19]. Before OGD, LBPs was administered at0, 100, 300 or 500 lg/ mL for 24 h [20].…”

DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways

“…Oxygen and glucose deprivation (OGD) of the neurons surrounding a hematoma has been considered a major factor in neuronal cell death in acute and chronic intracerebral hemorrhage (ICH) (Chien et al, 2015; Selim and Sheth, 2015; Korompoki et al, 2017). During an ICH, blood rushes into the surrounding brain tissue, at high pressure, resulting in brain damage from reduced regional cerebral blood flow in the perihematoma, and directly causing neuronal ischemia and hypoxia (Karaszewski et al, 2015; Rickards, 2015; Vavilis et al, 2015). Increasing evidences has shown that under OGD after ICH, protein misfolding and accumulation in the endoplasmic reticulum (ER) lumen initiate ER stress (Cominacini et al, 2015) and lead to mitochondrial apoptosis (Yuan et al, 2017).…”