Role of endoplasmic reticulum stress in ketamine-induced apoptosis in rat neurons: an in vitro experiment

Abstract

Objective To evaluate the role of endoplasmic reticulum stress in ketamine-induced apoptosis in rat neurons. Methods Rat adrenal pheochromocytoma cell line (PC12 cells) was seeded in the culture dishes 100 mm in diameter (10 ml/dish) or in 6-well plates (2 ml/well) at a density of 5 × 105 cells/ml.PC12 cells were divided into 4 groups (n=6 each) using a random number table: control group (group C); ketamine group (group K); endoplasmic reticulum stress inhibitor salubrinal group (group S); ketamine + salubrinal group (group K+ S). In group C, the cells were cultured in the plain culture medium.In group K, 1.5 mmol/L ketamine was added.In group S, 30 mmol/L salubrinal was added.In group K + S, 1.5 mmol/L ketamine and 30 mmol/L salubrinal were added.At 24 h of incubation, the cell morphology was observed under light microscope, the expression of Bip and caspase-12 in PC12 cells was detected by Western blot, and the cell apoptosis was measured by flow cytometry.The apoptosis rate was calculated. Results Compared with group C, the expression of Bip and caspase-12 was significantly up-regulated, and the apoptosis rate was increased in K and K+ S groups (P 0.05). Compared with group K, the expression of Bip and caspase-12 was significantly down-regulated, and the apoptosis rate was decreased in group K+ S (P<0.05). The degree of damage to PC12 cells was more serious in group K than in group C. The degree of damage to PC12 cells in group K+ S was significantly milder than that in group K and more serious than that in group C. Conclusion The mechanism by which ketamine induces neuronal apoptosis is related to the enhancement of endoplasmic reticulum stress in rats. Key words: Endoplasmic reticulum; Stress; Apotosis; Ketamine; PC12 cells