L-methionine sulfoximine interacted with propofol and showed toxicity in PC12 cells

Background: L-Methionine sulfoximine (MSO) inhibits glutamine synthesis in a rodent animal model, and its limited clinical use is implicitly associated with glutamate deprivation and neurotoxicity. The purpose of this experiment was to determine the effect of MSO on pheochromocytoma (PC12) cells and its interaction with propofol-induced neuro-apoptosis. Objective: To study the effects of MSO on cell viability following 100 μM propofol treatment and the impact of ribosomal S6 kinase 1 (RSK1) signaling on the PC12 cell line. Methods: PC12 cells were exposed to propofol-triggered neurotoxicity for 6 h and then subjected to MSO treatment. The gene and protein expression levels of members of the RSK1 signaling pathway were determined by real-time polymerase chain reaction, Western blot and histological analyses. The CCK8 test was used to assess cell viability, and cell proliferation and apoptosis were evaluated by flow cytometric analysis. Results: Propofol, a gamma-aminobutyric acid (GABA) agonist widely used in general anesthesia, significantly changed the expr ession level of cAMP response element-binding protein (CREB) and B cell lymphoma 2 (Bcl2) and solute carrier family 1 member 3 (Slc1a3), but not extracellular signal-regulated kinase 1/2 (ERK1/2). PC12 cells that were exposed to propofol for more than 6 h exhibited downregulation of RSK1. MSO aggravated the toxicity of propofol in PC12 cells via inhibition of the p90RSK1/CREB/Bcl2 signaling pathway.