Propofol pretreatment attenuates glutamate induced excitotoxicity of astrocytes via the p90RSK / Bcl-2 signaling pathway

Abstract

Propofol is a short acting anesthetic which can be used in neurosurgery and interventional surgery requiring anesthesia or sedation. Previous studies have suggested that glutamate has a toxic effect on astrocytes, while propofol has a protective effect on brain function. However, their mechanisms have not yet been elucidated. To determine the protective effect of propofol on brain function, we isolated primary astrocytes from the cerebral cortex of 1-day-old rats. After 10 days of culture, primary astrocytes were divided into control group (group C), propofol group (group P), glutamate group (group G), propofol + glutamate group (group PG), propofol + glutamate + inhibitor group (group PGI), and inhibitor group (group I). We then used the CCK8 assay method to test the effect of glutamate and propofol on astrocyte activity, and Western blot analysis to determine the expression of Caspase-3, Bcl-2, Bax, and p90RSK proteins. Moreover, flow cytometry was used to detect the level of apoptosis. Results showed that the expression of p90RSK and Bcl-2 was up-regulated in group P, while the expression of p90RSK and Bcl-2 was down-regulated and the expression of Bax and cleave-caspase3 were increased in group G. The expression of p90RSK and Bcl-2 were increased, while the expression of cleave-caspase3 was decreased in the PG group compared to the G group. In addition, the expression of p90RSK and Bcl-2 was decreased after PD98059 pretreatment. These results suggest that glutamate has a toxic effect on astrocytes, and propofol may attenuate the neurotoxicity of glutamate by activating the p90RSK / Bcl-2 signaling pathway.