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

AIM

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.

METHODS

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.

RESULTS

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 Ca 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, Ca and mitochondrial dysfunction.