The protective effect of propofol against TNF-α-induced apoptosis was mediated via inhibiting iNOS/NO production and maintaining intracellular Ca2+ homeostasis in mouse hippocampal HT22 cells

Inflammation cytokine tumor necrosis factor-α (TNF-α) induces apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF-α-induced apoptosis in mouse hippocampal HT22 cells and aimed to explore the underlying mechanisms.

We demonstrated that propofol could attenuate TNF-α-induced HT22 apoptosis. More importantly, we indicated that the underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.

Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with TNF-α. Cell viability was measured by cell counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis. The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit, intracellular calcium release and mitochondrial membrane potential (MMP) depolarization were measured by flow cytometry analysis, and the expression of inducible nitric oxide synthase (iNOS), C/EBP homologous protein (CHOP), B-cell lymphoma 2 (Bcl2) family and caspases were detected by Western blot.

Compared with control, TNF-α concentration- and time-dependently increased HT22 cell apoptosis, which was attenuated by 25μmol/l propofol. TNF-α (40ng/ml, 24h) induced the overexpression of iNOS and the release of nitric oxide, caused the accumulation of intracellular Ca2+ and endoplasmic reticulum (ER) stress, and therefore leading to mitochondrial dysfunction. Importantly, these effects were alleviated by 25μmol/l propofol. Conclusions: We demonstrated that propofol could attenuate TNF-α-induced HT22 apoptosis. More importantly, we indicated that the underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.